Distinct profiles of human B cell effector cytokines: a role in immune regulation?
There is growing interest in the fundamental roles that B cells may play in regulating immune responses. Emerging animal studies point to an important contribution of B cell effector cytokines to immune modulation, yet little is known about the factors regulating such cytokine production. We report that the profile of human B cell cytokine production is context dependent, being critically influenced by the balance of signals through the B cell receptor and CD40. B cells appropriately stimulated by sequential B cell receptor and CD40 stimulation proliferate and secrete TNF-alpha, lymphotoxin, and IL-6, which can act not only as autocrine growth and differentiation factors, but also serve to amplify the ongoing immune response. In contrast, CD40 stimulation alone, a mimic of a B cell receiving bystander T cell help in the absence of specific Ag recognition, induces negligible proinflammatory cytokines, but significant production of IL-10 that serves to suppress inappropriate immune responses. We thus describe a novel paradigm of reciprocal regulation of B cell effector cytokines, and ascribe active roles for human B cells in either promoting or suppressing local immune responses through context-dependent cytokine production.
Neuroimmunology Unit, Montreal Neurological Institute and McGill University, Montreal, Quebec, Canada.
Martin E
ME
Duddy
Andrea
A
Alter
Amit
A
Bar-Or
D000276:Adjuvants, Immunologic / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D024201:Bystander Effect / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D016207:Cytokines; D007106:Immune Sera; D018836:Inflammation Mediators; D011947:Receptors, Antigen, B-Cell; D016753:Interleukin-10