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

Abstract

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 by 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.