The role of IL-5 in IgA B cell differentiation

Abstract

IL-5 enhances secretion of IgA by B cells. The stage of B cell differentiation at which IL-5 enhances IgA secretion and the mechanism by which it exerts this effect are unknown. We examined these issues by separating Peyer's patch (PP) B cells into membrane IgA (mIgA)-positive and mIgA-negative cells with panning or cell sorting. When LPS was used to activate these cells, mIgA-positive PP B cells were induced by IL-5 (either as crude T cell supernatant or rIL-5 to secrete large amounts of IgA. In contrast mIgA-negative PP B cells showed no significant amount of IgA secretion with IL-5. In addition, rIL-5 did not cause expression of mIgA by mIgM-bearing B cells. The mechanism involved in enhancement of IgA secretion was evaluated by utilizing an ELISPOT assay to quantitate IgA secreting cells. Both unsorted PP B cells and mIgA-positive PP B cells, when incubated with IL-5, showed an increase in the number of IgA-secreting cells that was proportional to the increase in total secreted IgA. However, LPS-activated PP mIgA-positive B cells, when incubated with rIL-5, showed no increase in proliferation, as measured by [3H]thymidine incorporation indicating that the increase in IgA-secreting cells after incubation with IL-5 occurred not as a result of proliferation but rather through promotion of terminal differentiation. Thus, IL-5 acts as a differentiation factor on B cells which have already undergone isotype switch to IgA B cells, promoting differentiation into IgA-secreting cells with resultant increased IgA secretion.