Early B cell development requires μ signaling

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Abstract
In vitro studies with Abelson murine leukemia virus (AMuLV)‐transformed murine pre‐B cell lines demonstrated that wild‐type μ but not mutant μ chains lacking the first constant domain (μΔl) can efficiently induce Ig light (L) chain gene rearrangement. Using antibodies against the cytoplasmic tail of the immunoglobulin co‐receptor β (Igβ) chain we find μ., but not μA1 chains associated with Igμ. Since a heterodimer of surface‐labeled proteins was co‐precipitated with n we conclude that only wild‐type μ is associated with the Igα/Igβ co‐receptor on the surface of pre‐B cell lines. Mutant μΔ1 chains achieve their surface expression by utilizing a glycophospholipid anchor. In vivo analysis of transgenic mcie expressing either μ or μΔ1 transgenes revealed the expected “normal” B cell development in the case of wild‐type μ, transgenic lymphocytes, but a block in differentiation of μΔ1 transgenic lymphocytes. The maturation block occurs at the developmental transition of pre‐B lymphocytes from the CD43/S7+, CD45R/B220low stage to the CD43/S7−, B220low/hi8h stage in which the majority of L chain gene rearrangements occur. These results, together with the observed inability of the μΔ1 chains to signal activation of L chain gene joining and to associate Igα/Igβ in pre‐B cell lines suggest that signals mediated by the protein complex composed of μ/Igα/Igβ are crucial during differentiation of pre‐B lymphocytes.