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1172 Part IX: Lymphocytes and Plasma Cells Chapter 75: Functions of B Lymphocytes and Plasma Cells in Immunoglobulin Production 1173

that have B cells with a conditional deletion of IRF4 fail to generate 8. Niwa R, Natsume A, Uehara A, et al: IgG subclass-independent improvement of
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vate expression of Blimp-1. 112,120 Mice lacking such toll-like receptors 10. Horton RE, Vidarsson G: Antibodies and their receptors: Different potential roles in
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cannot mount effective antibody responses, except under certain 11. Wines BD, Hogarth PM: IgA receptors in health and disease. Tissue Antigens 68:103,
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conditions. Several cytokines, including IL-2, IL-5, IL-6, IL-10, and 2006.
IL-21, also can induce expression of Blimp-1 when applied in the proper 12. Novak J, Julian BA, Tomana M, Mestecky J: IgA glycosylation and IgA immune com-
context. Indeed, such cytokines can have positive or negative effects on plexes in the pathogenesis of IgA nephropathy. Semin Nephrol 28:78, 2008.
B-cell differentiation and/or survival depending upon the presence or 13. Sanders JT, Wyatt RJ: IgA nephropathy and Henoch-Schönlein purpura nephritis. Curr
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absence of other signals. IL-21, for example, can induce expression of 14. Yoo EM, Coloma MJ, Trinh KR, et al: Structural requirements for polymeric immuno-
Blimp-1 and plasma cell differentiation primarily in memory B cells or globulin assembly and association with J chain. J Biol Chem 274:33771, 1999.
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16. Chen K, Xu W, Wilson M, et al: Immunoglobulin D enhances immune surveillance
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T-cell helper signals, such as that caused by ligation of CD40. 123,124 On basophils. Nat Immunol 10:889, 2009.
the other hand, IL-21 can induce apoptosis of B cells that are activated 17. Roes J, Rajewsky K: Immunoglobulin D (IgD)-deficient mice reveal an auxiliary recep-
tor function for IgD in antigen-mediated recruitment of B cells. J Exp Med 177:45, 1993.
via ligation of its surface immunoglobulin receptor in the absence of 18. Lyczak JB, Zhang K, Saxon A, Morrison SL: Expression of novel secreted isoforms of
such T-cell helper signals. 124 human immunoglobulin E proteins. J Biol Chem 271:3428, 1996.
19. Tolar P, Hanna J, Krueger PD, Pierce SK: The constant region of the membrane immu-
noglobulin mediates B cell-receptor clustering and signaling in response to membrane
MEMORY B CELLS antigens. Immunity 30:44, 2009.
20. Wang Y, Kanegane H, Sanal O, et al: Novel Igalpha (CD79a) gene mutation in a Turkish
Following a T-cell dependent immune response to antigen, B cells that patient with B cell-deficient agammaglobulinemia. Am J Med Genet 108:333, 2002.
express high-affinity immunoglobulin for antigen also can differentiate 21. Carrasco YR, Batista FD: B cell recognition of membrane-bound antigen: An exquisite
into memory B cells. Memory B cells differ from plasma cells in mor- way of sensing ligands. Curr Opin Immunol 18:286, 2006.
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phology and function. In contrast to plasma cells, memory B cells do 22. Qi H, Egen JG, Huang AY, Germain RN: Extrafollicular activation of lymph node B cells
by antigen-bearing dendritic cells. Science 312:1672, 2006.
not secrete immunoglobulin, but rather express surface immunoglob- 23. Phan TG, Grigorova I, Okada T, Cyster JG: Subcapsular encounter and complement-
ulin that can bind antigen and can be induced to differentiate rapidly dependent transport of immune complexes by lymph node B cells. Nat Immunol 8:
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into immunoglobulin secreting plasma cells after secondary challenge 24. Junt T, Moseman EA, Iannacone M, et al: Subcapsular sinus macrophages in lymph
with antigen. Also, memory B cells may reengage the germinal center to nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450:110,
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ther the Ig repertoire. 126 25. Wu JN, Koretzky GA: The SLP-76 family of adapter proteins. Semin Immunol 16:379,
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Human memory B cells can be distinguished by their expression 26. Weber M, Treanor B, Depoil D, et al: Phospholipase C-gamma2 and Vav cooperate
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memory B cells lack expression of BCL-6, which actually can repress 30. Zhu C, Sato M, Yanagisawa T, et al: Novel binding site for Src homology 2-containing
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