IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis.
In these studies we determined the capacity of IL-6 to act as a differentiation cofactor for murine Peyer's patch B cells producing different Ig classes and subclasses. In preliminary studies we determined that sufficient endogenous IL-6 was produced in LPS-induced cell systems to obscure responses to exogenous IL-6. We therefore studied IL-6 effects on Peyer's patch B cells (T cell-depleted cell populations) in the absence of LPS, relying on responses of in vivo-activated cells. rIL-1 alpha or purified IL-6 only slightly enhanced synthesis of IgM over minimal baseline levels in Peyer's patch T cell-depleted cell cultures; however, when IL-6 was added to cultures also containing rIL-1, IgM synthesis was very substantially increased. In addition, rIL-5 alone gave rise to a modest increase in IgM synthesis and its effect was not enhanced by either rIL-1 or IL-6. IgG production (mainly IgG3) followed a similar pattern. In contrast, IgA production was only modestly increased above baseline by rIL-1, rIL-5, or IL-6 alone or by rIL-1 and IL-6 in combination, but was greatly increased by rIL-5 and IL-6 in combination. The effect of IL-6 on Ig synthesis in the above studies was not due to an effect on cell proliferation. In summary, these data indicate that B cells differ in respect to the cytokines supporting maximal terminal differentiation and thus the class of Ig produced may depend on the presence of a particular combination of cytokines and lymphokines.
Kunimoto
D Y
DY
Department of Medical Microbiology, University of Alberta, Edmonton, Canada.
Nordan
R P
RP
Strober
W
W
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000502:physiology*; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology; D013601:T-Lymphocytes
D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides