EARLY B-CELL DEVELOPMENT REQUIRES MU-SIGNALING

In vitro studies with Abelson murine leukemia virus (AMuLV)-transforme d murine pre-B cell lines demonstrated that wild-type mu but not mutan t mu chains lacking the first constant domain (muDELTA1) can efficient ly induce Ig light (L) chain gene rearrangement. Using antibodies agai nst the cytoplasmic tail of the immunoglobulin co-receptor beta (Igbet a) chain we find mu, but not muDELTA1 chains associated with Igbeta. S ince a heterodimer of surface-labeled proteins was co-precipitated wit h mu we conclude that only wild-type mu is associated with the Igalpha /Igbeta co-receptor on the surface of pre-B cell lines. Mutant muDELTA 1 chains achieve their surface expression by utilizing a glycophosphol ipid anchor. In vivo analysis of transgenic mcie expressing either mu or muDELTA1 transgenes revealed the expected ''normal'' B cell develop ment in the case of wild-type mu transgenic lymphocytes, but a block i n differentiation of muDELTA1 transgenic lymphocytes. The maturation b lock occurs at the developmental transition of pre-B lymphocytes from the CD43/S7+, CD45R/B220low stage to the CD43/S7-, B220low/high stage in which the majority of L chain gene rearrangements occur. These resu lts, together with the observed inability of the muDELTA1 chains to si gnal activation of L chain gene joining and to associate Igalpha/Igbet a in pre-B cell lines suggest that signals mediated by the protein com plex composed of mu/Igalpha/Igbeta are crucial during differentiation of pre-B lymphocytes.