IL4, IL5 and IL6-mediated regulation of immunoglobulin (Ig) heavy chain class switching and Ig production by gut-associated lymphoid tissue (GALT) B cells from athymic nude (nu/nu) mice.
Gut mucosal immunoglobulin (Ig) isotype expression and secretion are known to be regulated by B cell-stimulatory factors (BSF), lymphokines or cytokines from T and non-B cells. The class and amount of Ig secreted appear to depend on the presence of a combination of these factors. The effects of IL-4 and IL-5 on Ig class switching by gut mucosal B cells remain controversial. To shed further light on this issue, young (1-2 months old) athymic nu/nu murine GALT B cells were chosen, because the possibility of in vivo effects of T cells on B cells (in particular at the levels of transcription and translation without changes in surface Ig phenotype expression) cannot be excluded. The results are summarized below. IL-4, IL-5 and IL-6 alone or in combination do not act as IgA heavy chain switch cofactors, but IL-5 and IL-6 do act at least as B cell terminal differentiation factors for any isotype-specific gut-associated lymphoid tissue (GALT) (mesenteric lymph node) B cells in the presence or absence of LPS. The BSF have augmenting effects on class-specific Ig production by GALT sIgM-bearing B cells, when these are treated with the BSF alone. IL-4 alone or in combination with other BSF prevents LPS-stimulated IgM production. BSF without LPS do not evoke production of significant amounts of IgG and IgA by high density (HD) and low density (LD) sIgM-bearing B cells; IgM is synthesized only in small amounts of LD sIgM-bearing B cells in the presence of IL-5 and/or IL-6. There is no difference in the responsiveness of GALT and spleen sIgM-bearing B cells to the BSF.
Kawanishi
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Gut Mucosal Molecular Immunity Laboratory, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903.
Joseph
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007134:Immunoglobulin Switch Region; D007136:Immunoglobulins / Q000096:biosynthesis*; D016130:Immunophenotyping; D007378:Interleukins / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D007378:Interleukins