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研究生:邱奕凱
研究生(外文):Yi-Kai Chiu
論文名稱:轉錄因子ABF-1抑制漿細胞分化但是促進記憶B細胞形成
論文名稱(外文):Transcription Factor ABF-1 Suppresses Plasma Cell Differentiation but Facilitates Memory B Cell Formation
指導教授:林國儀
指導教授(外文):Kuo-I Lin
學位類別:博士
校院名稱:國立陽明大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:76
中文關鍵詞:漿細胞記憶B細胞生產中心B細胞轉錄抑制蛋白
外文關鍵詞:ABF-1Blimp-1plasma cellsmemory B cellsGC B cells
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ABF-1是的一個屬於bHLH家族的轉錄抑制蛋白, ABF-1表現在活化的B細胞以及霍奇金氏淋巴瘤細胞;ABF-1在霍奇金氏淋巴瘤的功能是經由拮抗E蛋白的功能因而抑制B細胞相關的基因;但是ABF-1在人類B細胞上的功能目前還是未知的。在之前的研究指出ABF-1受到轉錄抑制蛋白Blimp-1的調控。Blimp-1經由抑制已活化B細胞以及生長中心B細胞的基因來幫助漿細胞的分化。經由分析人類以及老鼠不同族群的B細胞發現ABF-1以及Msc (老鼠中ABF-1的直系同源基因) 基因主要表現在記憶B細胞,另外利用細胞介白素21以及刺激表面蛋白CD40來活化B細胞變成漿細胞的培養過程中,ABF-1以及Msc的表現先上升,隨著漿細胞的分化而下降。在培養B細胞變成漿細胞的過程中,利用慢病毒轉導表現ABF-1可抑制產生免疫球蛋白G漿細胞之分化,另外利用干擾RNA降低ABF-1的表現可以增加產生免疫球蛋白G漿細胞之分化。另外,我們發現ABF-1抑制活化B細胞的細胞增生進而抑制漿細胞分化。同樣的,利用cDNA微矩陣檢查被ABF-1所調控的基因,結果顯示在ABF-1大量表現的B細胞內,記憶B細胞相關的基因FCRL2和FCRL4表現會增加;然而與分泌抗體以及細胞增生相關的基因IGJ以及FLI1則被ABF-1抑制。此外,我們證明Blimp-1會直接黏結在ABF-1啟動子上面,進而抑制ABF-1基因的轉錄活性。
為了研究ABF-1在活體內的功能,我們生產了一株具B細胞表現專一性,而且需誘導活化ABF-1表現的EμVH-ABF-1-ER基因轉殖小鼠。在老鼠內打入特殊抗原而引起T細胞免疫反應的過程中誘發ABF-1的活性會減少具抗原專一性的漿細胞以及血液中對抗原有專一性抗體的量,這現象在免疫的二次反應也得到相同的結果。然而,在減少漿細胞的過程中,記憶B細胞的數量以及生產中心B細胞的數量是增加的,因此我們猜測ABF-1在生產中心B細胞分化成記憶B細胞的過程中扮演重要的角色。
總結,我們在活體外實驗以及活體內實驗都證實Blimp-1經由抑制ABF-1基因的表現以產生足夠數量的漿細胞;而ABF-1持續表現會促進記憶B細胞的分化。因此調節Blimp-1與ABF-1的軸向是決定已活化B細胞走向漿細胞或者記憶B細胞的重要關鍵。

ABF-1, a basic helix loop helix (bHLH) transcriptional repressor, is expressed in human activated B cells and Hodgkin’s lymphoma. The role of ABF-1 in Hodgkin’s lymphoma is to silence the expression of B cell specific genes by antagonizing E2A function. However, the function of ABF-1 in normal human B cells remains unclear up to date.
ABF-1 is a potential target of Blimp-1, which is a transcriptional repressor that inhibits gene expression program involved in activated B cells and germinal center B cells in order to facilitate plasma cell differentiation. Further analysis of ABF-1 and its mouse orthologue, Msc, expression in B cell subsets, showed that human and mouse memory B cells expressed higher ABF-1 or Msc than naïve B cells. ABF-1 was activated early in human memory B cells stimulated with IL-21 + αCD40 but was down-regulated in plasma cells. Ectopic expression of ABF-1 in IL-21 + αCD40-stimulated human memory B cells reduced IgG-secreting plasma cells, while knockdown of ABF-1 by shRNA generated more IgG-secreting plasma cells. The disturbed plasma cell generation by the levels of ABF-1 in the in vitro differentiation culture was linked with the changes in cell proliferation. Accordingly, microarray analysis of genes subjected to ABF-1 regulation revealed that FCRL2 and FCRL4 associated with memory B cells were up-regulated, whereas IGJ involved in immunoglobulin production and FLI1 involved in cell proliferation were down-regulated by ectopic expression of ABF-1. Furthermore, we demonstrated that ABF-1 was directly repressed by Blimp-1 that binds directly to the promoter region of ABF-1 and inhibits transcriptional activity of ABF-1.
To study the in vivo function of ABF-1, B cell-specific and inducible EμVH-ABF-1-ER transgenic mice were generated. Induction of ABF-1 in primary or secondary immune response results in reduced production of antigen-specific antibody and antigen-specific plasma cells. Furthermore, the population of germinal center B cells and memory B cells were amplified by induction of ABF-1 in primary immunization, suggesting ABF-1 may play a pivotal role in promoting germinal center B cells to become memory B cells.
In summary, we demonstrated that Blimp-1-mediated ABF-1 repression was required for plasmacytic differentiation in vitro and in vivo. Thus, the regulatory axis of Blimp-1 and ABF-1 may decide the fate of activated B cells to become either plasma cells or memory B cells.

Contents

Chapter 1
Introduction 1
1.1 HLH proteins and B lymphocyte development 1
1.2 ABF-1, a transcriptional repressor in activated human B
cells 2
1.3 Priming of B cells 3
1.4 GC reaction
4
1.5 Memory B cell and antigen recall response 6
1.6 Blimp-1, a master regulator of plasma cell
differentiation 6
1.7 Repression of mature B cell genes by Blimp-1 in plasma
cell differentiation 9
1.8 Specific aim 9

Chapter 2 Materials and Methods 11
2.1 Cell culture and reagents 11
2.2 Plasmid 12
2.3 Generation of EμVH-ABF-1-estrogen receptor transgenic mice 12
2.4 Immunization, BrdU labeling and adoptive transfer study
13
2.5 Generation of lentivirus and viral transduction 14
2.6 RNA isolation and RT-quantitative PCR (RT-QPCR) 14
2.7 Immunoblotting 15
2.8 Chromatin immunoprecipitation (ChIP) 15
2.9 DNA pull-down assay and EMSA 16
2.10 Transfection and luciferase reporter assay 16
2.11 ELISA and ELISPOT assays 18
2.12 Propidium iodide (PI) staining 18
2.13 Apoptotic assay 19
2.14 Flow cytometry 19
2.15 Immunohistochemistry 20
2.16 Microarray 20

Chapter 3 Results 22
3.1 ABF-1 is expressed in human memory B cell and activated B cells but is repressed in plasma cells 22
3.2 Ectopic expression of ABF-1 in B cells inhibits the differentiation of antibody secreting plasma cells 22
3.3 Knockdown of ABF-1 by shRNA enhances plasma cell differentiation 23
3.4 ABF-1 arrests B cell expansion 24
3.5 ABF-1 regulates genes in transcription network of plasma cell differentiation 24
3.6 Identification of genes in B cells associated with enhanced ABF-1 expression 25
3.7 ABF-1 expression was correlated with cell cycle status and was repressed by Blimp-1 26
3.8 Blimp-1 directly represses ABF-1 26
3.9 Msc, an ortholog of ABF-1 in mice, is expressed in GC B cells, memory B cells and activated B cells in response to T-dependent stimulation 28
3.10 Induction of ABF-1 in primary response enhances GC formation and the generation of antigen specific memory B cells 29
3.11 Induction of ABF-1 repressed plasma cell formation in primary immunization 31
3.12 Induction of ABF-1 during Ag recall blocks plasma cell formation 31
3.13 Secondary immune responses in ABF-1 ITG mice 32

Chapter 4 Discussion 34
4.1 Regulation of plasmacytic differentiation by ABF-1 34
4.2 Blimp-1 directly represses ABF-1 35
4.3 Mechanism of ABF-1 in repressing plasmacytic differentiation 36
4.4 In vivo study of ABF-1’s function 39
4.5 Conclusion 43

Chapter 5 References 45

Figure content

FIGURE 1. Expression of ABF-1 and Blimp-1 in stimulated human peripheral B cells 54
FIGURE 2. Enforced expression of ABF-1 represses IgM secretion 55
FIGURE 3. Enforced expression of ABF-1 represses plasma cell differentiation 56
FIGURE 4. shRNA knockdown ABF-1 assists plasmacytic differentiation 57
FIGURE 5. ABF-1 regulates cell proliferation, but not cell survival 58
FIGURE 6. Identification of ABF-1 downstream genes 59
FIGURE 7. Identification of ABF-1 downstream genes by cDNA microarray 60
FIGURE 8. Expression of ABF-1 is inversely correlated with Blimp-1 expression 61
FIGURE 9. Blimp-1 directly suppresses ABF-1 62
FIGURE 10. Blimp-1 directly suppresses ABF-1 63
FIGURE 11. Msc is induced by TFH-mediated signals 64
FIGURE 12. NF-κB signaling is required for Msc expression
65
FIGURE 13. B cell development and ABF-1-ER expression in ABF-1-ER transgenic mice 66
FIGURE 14. Induction of ABF-1 in vivo alters GC B cell formation 67
FIGURE 15. Induction of ABF-1 in vivo alters memory B cell formation 69
FIGURE 16. Induction of ABF-1 in vivo prevents plasma cell formation 70
FIGURE 17. Induction of ABF-1 doesn’t interfere IgM secretion, CSR and IgG affinity 71
FIGURE 18. Induction of ABF-1 during Ag recall blocks plasma cell formation 72
FIGURE 19. Memory B cells of ITG mice induced more antibody-secreting plasma cells 73
FIGURE 20. Proposed model of the functions of ABF-1 in determining plasma cell and memory B cell differentiation
74

Table content

Table I. Genes that are down-regulated by more than 2-fold in SKW B cells that overexpress ABF-1 75
Table II. Genes that are up-regulated by more than 2-fold in SKW B cells that overexpress ABF-1 76

Adolfsson, J., R. Mansson, N. Buza-Vidas, A. Hultquist, K. Liuba, C.T. Jensen, D. Bryder, L. Yang, O.J. Borge, L.A. Thoren, K. Anderson, E. Sitnicka, Y. Sasaki, M. Sigvardsson, and S.E. Jacobsen. 2005. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121:295-306.

Allen, C.D., T. Okada, H.L. Tang, and J.G. Cyster. 2007. Imaging of germinal center selection events during affinity maturation. Science 315:528-531.

Bain, G., E.C. Maandag, D.J. Izon, D. Amsen, A.M. Kruisbeek, B.C. Weintraub, I. Krop, M.S. Schlissel, A.J. Feeney, M. van Roon, and et al. 1994. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 79:885-892.

Batista, F.D., and N.E. Harwood. 2009. The who, how and where of antigen presentation to B cells. Nature reviews. Immunology 9:15-27.

Benezra, R., R.L. Davis, D. Lockshon, D.L. Turner, and H. Weintraub. 1990. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61:49-59.

Blackman, M.A., M.A. Tigges, M.E. Minie, and M.E. Koshland. 1986. A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain gene. Cell 47:609-617.

Bradshaw, S., W.J. Zheng, L.C. Tsoi, G. Gilkeson, and X.K. Zhang. 2008. A role for Fli-1 in B cell proliferation: implications for SLE pathogenesis. Clinical immunology 129:19-30.

Butcher, E.C., R.V. Rouse, R.L. Coffman, C.N. Nottenburg, R.R. Hardy, and I.L. Weissman. 1982. Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation. Journal of immunology 129:2698-2707.

Chan, Y.H., M.F. Chiang, Y.C. Tsai, S.T. Su, M.H. Chen, M.S. Hou, and K.I. Lin. 2009. Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function. Journal of immunology 183:7039-7046.

Chiang, M.F., S.Y. Yang, I.Y. Lin, J.B. Hong, S.J. Lin, H.Y. Ying, C.M. Chen, S.Y. Wu, F.T. Liu, and K.I. Lin. 2013. Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice. Proceedings of the National Academy of Sciences of the United States of America 110:6476-6481.

Cimmino, L., G.A. Martins, J. Liao, E. Magnusdottir, G. Grunig, R.K. Perez, and K.L. Calame. 2008. Blimp-1 attenuates Th1 differentiation by repression of ifng, tbx21, and bcl6 gene expression. Journal of immunology 181:2338-2347.

Davis, R.S. 2007. Fc receptor-like molecules. Annual review of immunology 25:525-560.

Delogu, A., A. Schebesta, Q. Sun, K. Aschenbrenner, T. Perlot, and M. Busslinger. 2006. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity 24:269-281.

Dent, A.L., A.L. Shaffer, X. Yu, D. Allman, and L.M. Staudt. 1997. Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276:589-592.

Di Noia, J.M., and M.S. Neuberger. 2007. Molecular mechanisms of antibody somatic hypermutation. Annual review of biochemistry 76:1-22.

Ehrhardt, G.R., J.T. Hsu, L. Gartland, C.M. Leu, S. Zhang, R.S. Davis, and M.D. Cooper. 2005. Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells. The Journal of experimental medicine 202:783-791.

Ema, H., Y. Morita, and T. Suda. 2014. Heterogeneity and hierarchy of hematopoietic stem cells. Experimental hematology 42:74-82 e72.

Ettinger, R., G.P. Sims, A.M. Fairhurst, R. Robbins, Y.S. da Silva, R. Spolski, W.J. Leonard, and P.E. Lipsky. 2005. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. Journal of immunology 175:7867-7879.

Falini, B., E. Tiacci, A. Pucciarini, B. Bigerna, J. Kurth, G. Hatzivassiliou, S. Droetto, B.V. Galletti, M. Gambacorta, A. Orazi, L. Pasqualucci, I. Miller, R. Kuppers, R. Dalla-Favera, and G. Cattoretti. 2003. Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). Blood 102:3684-3692.

Forster, I. 2004. Analysis of B-cell life-span and homeostasis. Methods in molecular biology 271:59-66.

Giesecke, C., D. Frolich, K. Reiter, H.E. Mei, I. Wirries, R. Kuhly, M. Killig, T. Glatzer, K. Stolzel, C. Perka, P.E. Lipsky, and T. Dorner. 2014. Tissue distribution and dependence of responsiveness of human antigen-specific memory B cells. Journal of immunology 192:3091-3100.

Goldstein, H., D. Koerholz, L. Chesky, X.D. Fan, and J.L. Ambrus, Jr. 1990. Divergent activities of protein kinases in IL-6-induced differentiation of a human B cell line. Journal of immunology 145:952-961.

Gonda, H., M. Sugai, Y. Nambu, T. Katakai, Y. Agata, K.J. Mori, Y. Yokota, and A. Shimizu. 2003. The balance between Pax5 and Id2 activities is the key to AID gene expression. The Journal of experimental medicine 198:1427-1437.

Gyory, I., J. Wu, G. Fejer, E. Seto, and K.L. Wright. 2004. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nature immunology 5:299-308.

Inamine, A., Y. Takahashi, N. Baba, K. Miyake, T. Tokuhisa, T. Takemori, and R. Abe. 2005. Two waves of memory B-cell generation in the primary immune response. International immunology 17:581-589.

Jourdan, M., A. Caraux, J. De Vos, G. Fiol, M. Larroque, C. Cognot, C. Bret, C. Duperray, D. Hose, and B. Klein. 2009. An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization. Blood 114:5173-5181.

Kaji, T., A. Ishige, M. Hikida, J. Taka, A. Hijikata, M. Kubo, T. Nagashima, Y. Takahashi, T. Kurosaki, M. Okada, O. Ohara, K. Rajewsky, and T. Takemori. 2012. Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. The Journal of experimental medicine 209:2079-2097.

Kallies, A., J. Hasbold, K. Fairfax, C. Pridans, D. Emslie, B.S. McKenzie, A.M. Lew, L.M. Corcoran, P.D. Hodgkin, D.M. Tarlinton, and S.L. Nutt. 2007. Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1. Immunity 26:555-566.

Kee, B.L. 2009. E and ID proteins branch out. Nature reviews. Immunology 9:175-184.

Kee, B.L., M.W. Quong, and C. Murre. 2000. E2A proteins: essential regulators at multiple stages of B-cell development. Immunological reviews 175:138-149.

Keller, A.D., and T. Maniatis. 1991. Identification and characterization of a novel repressor of beta-interferon gene expression. Genes & development 5:868-879.

King, C., S.G. Tangye, and C.R. Mackay. 2008. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annual review of immunology 26:741-766.

Klein, U., and R. Dalla-Favera. 2008. Germinal centres: role in B-cell physiology and malignancy. Nature reviews. Immunology 8:22-33.

Klein, U., K. Rajewsky, and R. Kuppers. 1998. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. The Journal of experimental medicine 188:1679-1689.

Kondo, M., I.L. Weissman, and K. Akashi. 1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661-672.

Koshland, M.E. 1985. The coming of age of the immunoglobulin J chain. Annual review of immunology 3:425-453.

Kuo, T.C., and K.L. Calame. 2004. B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. Journal of immunology 173:5556-5563.

Kuo, T.C., A.L. Shaffer, J. Haddad, Jr., Y.S. Choi, L.M. Staudt, and K. Calame. 2007. Repression of BCL-6 is required for the formation of human memory B cells in vitro. The Journal of experimental medicine 204:819-830.

Kwon, K., C. Hutter, Q. Sun, I. Bilic, C. Cobaleda, S. Malin, and M. Busslinger. 2008. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity 28:751-762.

Lee, C.H., M. Melchers, H. Wang, T.A. Torrey, R. Slota, C.F. Qi, J.Y. Kim, P. Lugar, H.J. Kong, L. Farrington, B. van der Zouwen, J.X. Zhou, V. Lougaris, P.E. Lipsky, A.C. Grammer, and H.C. Morse, 3rd. 2006. Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. The Journal of experimental medicine 203:63-72.

Lin, K.I., C. Angelin-Duclos, T.C. Kuo, and K. Calame. 2002. Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells. Molecular and cellular biology 22:4771-4780.
Lin, Y., K. Wong, and K. Calame. 1997. Repression of c-myc transcription by Blimp-1, an inducer of terminal B cell differentiation. Science 276:596-599.

Lindeman, G.J., A.W. Harris, M.L. Bath, R.N. Eisenman, and J.M. Adams. 1995. Overexpressed max is not oncogenic and attenuates myc-induced lymphoproliferation and lymphomagenesis in transgenic mice. Oncogene 10:1013-1017.

Lu, J., R. Webb, J.A. Richardson, and E.N. Olson. 1999. MyoR: a muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD. Proceedings of the National Academy of Sciences of the United States of America 96:552-557.

Martins, G., and K. Calame. 2008. Regulation and functions of Blimp-1 in T and B lymphocytes. Annual review of immunology 26:133-169.

Massari, M.E., R.R. Rivera, J.R. Voland, M.W. Quong, T.M. Breit, J.J. van Dongen, O. de Smit, and C. Murre. 1998. Characterization of ABF-1, a novel basic helix-loop-helix transcription factor expressed in activated B lymphocytes. Molecular and cellular biology 18:3130-3139.

Mathas, S., M. Janz, F. Hummel, M. Hummel, B. Wollert-Wulf, S. Lusatis, I. Anagnostopoulos, A. Lietz, M. Sigvardsson, F. Jundt, K. Johrens, K. Bommert, H. Stein, and B. Dorken. 2006. Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma. Nature immunology 7:207-215.

McHeyzer-Williams, L.J., M. Cool, and M.G. McHeyzer-Williams. 2000. Antigen-specific B cell memory: expression and replenishment of a novel b220(-) memory b cell compartment. The Journal of experimental medicine 191:1149-1166.

McHeyzer-Williams, L.J., and M.G. McHeyzer-Williams. 2005. Antigen-specific memory B cell development. Annual review of immunology 23:487-513.

McHeyzer-Williams, M., S. Okitsu, N. Wang, and L. McHeyzer-Williams. 2012. Molecular programming of B cell memory. Nature reviews. Immunology 12:24-34.

Moir, S., J. Ho, A. Malaspina, W. Wang, A.C. DiPoto, M.A. O'Shea, G. Roby, S. Kottilil, J. Arthos, M.A. Proschan, T.W. Chun, and A.S. Fauci. 2008. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. The Journal of experimental medicine 205:1797-1805.

Mora-Lopez, F., E. Reales, J.A. Brieva, and A. Campos-Caro. 2007. Human BSAP and BLIMP1 conform an autoregulatory feedback loop. Blood 110:3150-3157.

Murre, C. 2005. Helix-loop-helix proteins and lymphocyte development. Nature immunology 6:1079-1086.

Muto, A., S. Tashiro, O. Nakajima, H. Hoshino, S. Takahashi, E. Sakoda, D. Ikebe, M. Yamamoto, and K. Igarashi. 2004. The transcriptional programme of antibody class switching involves the repressor Bach2. Nature 429:566-571.

Nutt, S.L. 2008. B-cell identity--commitment is not forever. The New England journal of medicine 358:82-83.

O'Riordan, M., and R. Grosschedl. 1999. Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A. Immunity 11:21-31.

Ochiai, K., Y. Katoh, T. Ikura, Y. Hoshikawa, T. Noda, H. Karasuyama, S. Tashiro, A. Muto, and K. Igarashi. 2006. Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells. The Journal of biological chemistry 281:38226-38234.

Odegard, V.H., and D.G. Schatz. 2006. Targeting of somatic hypermutation. Nature reviews. Immunology 6:573-583.

Ohinata, Y., B. Payer, D. O'Carroll, K. Ancelin, Y. Ono, M. Sano, S.C. Barton, T. Obukhanych, M. Nussenzweig, A. Tarakhovsky, M. Saitou, and M.A. Surani. 2005. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436:207-213.

Ozaki, K., R. Spolski, R. Ettinger, H.P. Kim, G. Wang, C.F. Qi, P. Hwu, D.J. Shaffer, S. Akilesh, D.C. Roopenian, H.C. Morse, 3rd, P.E. Lipsky, and W.J. Leonard. 2004. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. Journal of immunology 173:5361-5371.

Pedersen, I.M., S. Kitada, L.M. Leoni, J.M. Zapata, J.G. Karras, N. Tsukada, T.J. Kipps, Y.S. Choi, F. Bennett, and J.C. Reed. 2002. Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1. Blood 100:1795-1801.

Phan, T.G., D. Paus, T.D. Chan, M.L. Turner, S.L. Nutt, A. Basten, and R. Brink. 2006. High affinity germinal center B cells are actively selected into the plasma cell compartment. The Journal of experimental medicine 203:2419-2424.

Piskurich, J.F., K.I. Lin, Y. Lin, Y. Wang, J.P. Ting, and K. Calame. 2000. BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells. Nature immunology 1:526-532.

Qin, X.F., D.S. An, I.S. Chen, and D. Baltimore. 2003. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proceedings of the National Academy of Sciences of the United States of America 100:183-188.

Quong, M.W., D.P. Harris, S.L. Swain, and C. Murre. 1999. E2A activity is induced during B-cell activation to promote immunoglobulin class switch recombination. The EMBO journal 18:6307-6318.

Rakhmanov, M., H. Sic, A.K. Kienzler, B. Fischer, M. Rizzi, M. Seidl, K. Melkaoui, S. Unger, L. Moehle, N.E. Schmit, S.D. Deshmukh, C.K. Ayata, W. Schuh, Z. Zhang, F.L. Cosset, E. Verhoeyen, H.H. Peter, R.E. Voll, U. Salzer, H. Eibel, and K. Warnatz. 2014. High Levels of SOX5 Decrease Proliferative Capacity of Human B Cells, but Permit Plasmablast Differentiation. PloS one 9:e100328.

Reimold, A.M., P.D. Ponath, Y.S. Li, R.R. Hardy, C.S. David, J.L. Strominger, and L.H. Glimcher. 1996. Transcription factor B cell lineage-specific activator protein regulates the gene for human X-box binding protein 1. The Journal of experimental medicine 183:393-401.

Ren, B., K.J. Chee, T.H. Kim, and T. Maniatis. 1999. PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins. Genes & development 13:125-137.
Rinkenberger, J.L., J.J. Wallin, K.W. Johnson, and M.E. Koshland. 1996. An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the immunoglobulin J chain gene. Immunity 5:377-386.

Sayegh, C.E., M.W. Quong, Y. Agata, and C. Murre. 2003. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nature immunology 4:586-593.

Schmidlin, H., S.A. Diehl, M. Nagasawa, F.A. Scheeren, R. Schotte, C.H. Uittenbogaart, H. Spits, and B. Blom. 2008. Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression. Blood 112:1804-1812.

Shaffer, A.L., K.I. Lin, T.C. Kuo, X. Yu, E.M. Hurt, A. Rosenwald, J.M. Giltnane, L. Yang, H. Zhao, K. Calame, and L.M. Staudt. 2002. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17:51-62.

Shaffer, A.L., X. Yu, Y. He, J. Boldrick, E.P. Chan, and L.M. Staudt. 2000. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 13:199-212.

Shapiro-Shelef, M., and K. Calame. 2005. Regulation of plasma-cell development. Nature reviews. Immunology 5:230-242.

Shapiro-Shelef, M., K.I. Lin, L.J. McHeyzer-Williams, J. Liao, M.G. McHeyzer-Williams, and K. Calame. 2003. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19:607-620.

Shapiro-Shelef, M., K.I. Lin, D. Savitsky, J. Liao, and K. Calame. 2005. Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow. The Journal of experimental medicine 202:1471-1476.

Su, G.H., H.M. Chen, N. Muthusamy, L.A. Garrett-Sinha, D. Baunoch, D.G. Tenen, and M.C. Simon. 1997. Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B. The EMBO journal 16:7118-7129.

Su, S.T., H.Y. Ying, Y.K. Chiu, F.R. Lin, M.Y. Chen, and K.I. Lin. 2009. Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation. Molecular and cellular biology 29:1421-1431.

Taylor, J.J., K.A. Pape, and M.K. Jenkins. 2012. A germinal center-independent pathway generates unswitched memory B cells early in the primary response. The Journal of experimental medicine 209:597-606.

Tormo, A.J., Y. Meliani, L.A. Beaupre, M. Sharma, J.H. Fritz, G. Elson, S. Crabe, and J.F. Gauchat. 2013. The composite cytokine p28/cytokine-like factor 1 sustains B cell proliferation and promotes plasma cell differentiation. Journal of immunology 191:1657-1665.

Toyama, H., S. Okada, M. Hatano, Y. Takahashi, N. Takeda, H. Ichii, T. Takemori, Y. Kuroda, and T. Tokuhisa. 2002. Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 17:329-339.

Tung, J.W., D.R. Parks, W.A. Moore, L.A. Herzenberg, and L.A. Herzenberg. 2004. Identification of B-cell subsets: an exposition of 11-color (Hi-D) FACS methods. Methods in molecular biology 271:37-58.

Tunyaplin, C., A.L. Shaffer, C.D. Angelin-Duclos, X. Yu, L.M. Staudt, and K.L. Calame. 2004. Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation. Journal of immunology 173:1158-1165.

Turner, C.A., Jr., D.H. Mack, and M.M. Davis. 1994. Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 77:297-306.

Wang, N.S., L.J. McHeyzer-Williams, S.L. Okitsu, T.P. Burris, S.L. Reiner, and M.G. McHeyzer-Williams. 2012. Divergent transcriptional programming of class-specific B cell memory by T-bet and RORalpha. Nature immunology 13:604-611.

Wong, J., M. Funes-Duran, J. Ahlberg, J. Round, R. O'Connell, R. Miller, E. Chen, P.A. Richmond, and C.A. Vierra. 2001. Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2. DNA and cell biology 20:465-471.

Yeo, L., H. Lom, M. Juarez, M. Snow, C.D. Buckley, A. Filer, K. Raza, and D. Scheel-Toellner. 2014. Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Annals of the rheumatic diseases

Ying, H.Y., S.T. Su, P.H. Hsu, C.C. Chang, I.Y. Lin, Y.H. Tseng, M.D. Tsai, H.M. Shih, and K.I. Lin. 2012. SUMOylation of Blimp-1 is critical for plasma cell differentiation. EMBO reports 13:631-637.

Yoshida, H., T. Matsui, A. Yamamoto, T. Okada, and K. Mori. 2001. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881-891.

Yu, J., C. Angelin-Duclos, J. Greenwood, J. Liao, and K. Calame. 2000. Transcriptional repression by blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Molecular and cellular biology 20:2592-2603.

Yu, L., J. Mikloucich, N. Sangster, A. Perez, and P.J. McCormick. 2003. MyoR is expressed in nonmyogenic cells and can inhibit their differentiation. Experimental cell research 289:162-173.

Zabel, F., D. Mohanan, J. Bessa, A. Link, A. Fettelschoss, P. Saudan, T.M. Kundig, and M.F. Bachmann. 2014. Viral particles drive rapid differentiation of memory B cells into secondary plasma cells producing increased levels of antibodies. Journal of immunology 192:5499-5508.

Zhang, X.K., O. Moussa, A. LaRue, S. Bradshaw, I. Molano, D.D. Spyropoulos, G.S. Gilkeson, and D.K. Watson. 2008. The transcription factor Fli-1 modulates marginal zone and follicular B cell development in mice. Journal of immunology 181:1644-1654.

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