title: CD80 expression on B cells regulates murine T follicular helper development, germinal center B cell survival, and plasma cell generation.
abstract: Germinal center (GC) B cells and T follicular helper (T(FH)) cells interact in the production of high-affinity long-lived plasma cells (PCs) and memory B cells, although the mechanisms regulating the formation of these long-lived populations remain unclear. Because CD80 is one of the few markers shared by human and murine memory B cells, we investigated its role in the development of GCs, memory cells, and PCs. In CD80-deficient mice, fewer long-lived PCs were generated upon immunization compared with that in B6 controls. In concert, the absence of CD80 resulted in an increase in apoptotic GC B cells during the contraction phase of the GC. CD80(-/-) mice had fewer T(FH) cells compared with that of B6, and residual T(FH) cells failed to mature, with decreased ICOS and PD-1 expression and decreased synthesis of IL-21 mRNA. Mixed bone marrow chimeras demonstrated a B cell-intrinsic requirement for CD80 expression for normal T(FH) cell and PC development. Therefore, B cell expression of CD80 plays a critical role in regulating B-T interactions in both early and late GC responses. This, in turn, results in impaired ability to produce long-lived PCs. These data provide new insights into the development of GCs and Ab-forming cells and the functions of CD80 in humoral immunity.
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT 06519, USA.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Good-Jacobson
authors.forename: Eunice
authors.initials: E
authors.lastname: Song
authors.forename: Shannon
authors.initials: S
authors.lastname: Anderson
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D000943:Antigens, Differentiation; D018122:B7-1 Antigen; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D000098546:Interleukin-21