Increased IL-12 inhibits B cells' differentiation to germinal center cells and promotes differentiation to short-lived plasmablasts.
B cells activated by antigen in T cell-dependent immune responses can become short-lived plasma cells, which remain in the spleen, or germinal center-derived memory or plasma cells, which show evidence of affinity maturation and, in the case of plasma cells, migrate to the bone marrow. We show that this cell fate decision can be governed by the cytokine environment engendered by activated dendritic cells (DCs). DCs from mice lacking the Fc receptor gamma chain exhibited an activated phenotype in vitro. They secreted more of the proinflammatory cytokine IL-12, which led to the preferential generation of short-lived splenic plasma cells, with ensuing low affinity antibodies and a diminished recall response. Understanding the factors that regulate antigen-activated B cell differentiation and memory cell formation has implications for both antibody-mediated autoimmune disease and protective antibody responses.
Kim
Sun Jung
SJ
Autoimmune Disease Laboratory, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Caton
Michele
M
Wang
Chuansheng
C
Khalil
Magi
M
Zhou
Zhi-Jie
ZJ
Hardin
John
J
Diamond
Betty
B
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000502:physiology*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D000941:Antigens; D017452:Receptors, IgG; D018664:Interleukin-12