Regulation of isotype production by IL-4 and IL-5. Effects of lymphokines on Ig production depend on the state of activation of the responding B cells.
The effects of IL-4 and IL-5 on the production of Ig of different isotypes was investigated. We compared B cells from spleen and from Peyer's patches either stimulated with LPS or without added polyclonal stimulation. We also compared high density (small) and low density (large) B cells. The effect of lymphokines depended on the size and source of the B cells as well as on whether LPS was added. As expected, small B cells from either lymphoid compartment responded to LPS alone and IL-4 suppressed IgM and IgG3 production and enhanced IgG1. In contrast, when large B cells were examined, the suppressive effects of IL-4 were much less apparent but the enhancement of IgG1 was still marked. IL-5 alone had only minimal effects in LPS-stimulated cultures but the combination of IL-4 plus IL-5 appeared to overcome much of the IL-4-mediated suppression of IgM, and IgA production was enhanced. In the absence of LPS, a quite different profile is seen. First, small B cells make little if any response. Second, there is dramatic synergy between IL-4 and IL-5 in the response of large B cells, which is independent of isotype. Third, IL-4 does not suppress any isotype in the absence of LPS. Fourth, IL-4 plus IL-5 stimulate large Peyer's patch B cells to produce 10 times more IgA but three times less IgM than large spleen B cells. Fifth, Th2 cells directly stimulate both large and small B cells.
Tonkonogy
S L
SL
Department of Microbiology, Pathology and Parasitology, University of North Carolina Core Center in Diarrheal Diseases, Raleigh 27606.
McKenzie
D T
DT
Swain
S L
SL
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4; D015848:Interleukin-5; D007378:Interleukins / Q000502:physiology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D015848:Interleukin-5; D007378:Interleukins; D015847:Interleukin-4