Effects of transforming growth factor .betha.1 and interleukin-2 on IgA isotype switching at the clonal level

IgA is the predominant immunoglobulin isotype in mucosal secretions(1). It has been reported that a population of Peyer's patch T cells can selectively induce IgM bearing B cells to switch to surface IgA bearing B cells(2,3). Further, IL-4, IL-5, and IL-6 alone and in combination, can significantly influence murine IgA B cell differentiation in vitro(4-7). However, it remains an open question which cytokines have a major role in class switching to the IgA isotype. Recently, it has been reported that transforming growth factor .betha.1(TGF .betha.1) alone, or in combination with IL-2 increases IgA secretion by LPS-activated surface IgA negative (sIgA$\^$-/) murine spleen B cells while concurrently downregulating IgM and IgG secretion by such cells(8-11). In the present study, limiting dilution analysis was used to demonstrate, at the clonal level, that TGF .betha.1 has siginificant activity as an IgA isotype switch factor.