Immature B lymphocytes are deficient in expression of the src-family kinases p59fyn and p55fgr1.

Abstract

Unlike mature B cells, immature B cells are highly sensitive to tolerance induction and do not proliferate in response to stimulation through their Ag receptors. Our previous studies have suggested that this differential responsiveness is caused by differences in Ag receptor-proximal signaling pathways. Because many of these pathways are regulated by tyrosine phosphorylation, we have compared the expression and activity of tyrosine kinases in immature and mature B cells. Consistent with previous studies, we demonstrate that mature B cells express syk, lyn, blk, hck, and fyn; in addition, we find that they express significant amounts of the src-family kinase p55fgr. Immature B cells from day-3 mouse spleen show similar expression and activity of syk, lyn, blk, and hck. However, these cells have marked deficiencies in fyn and fgr expression. Differential expression of fyn and fgr is also observed in immature cells from the bone marrow, indicating that this phenotype is characteristic of the immature stage of B cell development. High levels of fyn and fgr are detectable in splenic B cells beginning at 4 wk of age, coincident with the appearance of cells that proliferate in response to receptor cross-linking. These observations indicate that expression of the src-family kinases fyn and fgr is regulated developmentally in murine B lymphocytes. Moreover, they suggest that these kinases may be important for mature B cell responses to Ag receptor stimulation, and that their absence may contribute to the unresponsiveness and tolerance susceptibility of immature B cells.