Normal B cells fail to secrete interleukin‐12

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Abstract
Interleukin‐12 is a key regulatory cytokine produced by antigen‐presenting cells (APC) which drives the development of interferon‐γ (IFN‐γ)‐producing cells and promotes cell‐mediated immunity. Following subcutaneous immunization with protein antigen in adjuvant, dendritic cells (DC) but not small nor large B cells in immune lymph nodes express antigenic complexes and secrete substantial amounts of bioactive IL‐12 p75 upon antigen‐specific interaction with T cells. We have analyzed secretion of IL‐12 p40 and p75 by cell populations enriched in DC, macrophages or B cells in response to nonspecific stimulation or to interaction with antigen‐specific CD4+ cells. These APC populations do not produce IL‐12 constitutively but, upon stimulation with heat‐fixed Staphylococcus aureus and IFN‐γ, IL‐12 p40 and p75 are secreted by DC and macrophages, whereas B cells fail to produce IL‐12. B cells also fail to secrete IL‐12 in response to stimulation with LPS and IFN‐γ. Co‐culture with CD4+ T hybridoma cells and antigen induces IL‐12 secretion by DC. Up‐regulation of IL‐12 secretion by interaction with antigen‐specific CD4+ T cells is abrogated by anti‐class II monoclonal antibodies (mAb), by soluble CD40 molecules and by anti‐CD40 ligand mAb, demonstrating a positive feedback between T cells and DC mediated by TCR‐peptide/class II and by CD40‐CD40 ligand interactions. Expression of class II and CD40 molecules is comparable in B cells and DC, and both APC types activate CD4+ T cells. Yet, even upon interaction with antigen‐specific T cells, B cells fail to secrete IL‐12. The capacity of B cells to present antigen but not to secrete IL‐12 may explain their propensity to selectively drive T helper type 2 cell development.

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