Structural and quantitative differences between membrane μ chains associated with surrogate or conventional light chains (45.1)

Abstract

Abstract Although it is well established that pre-BCR signaling governs proliferation and differentiation during B cell development, the components of the pre-BCR that are important for signaling are a matter of controversy. It has been suggested that signaling by the µ heavy chains (μHC) of the pre-BCR induces survival and differentiation, while the surrogate light chains (SLC) are essential for proliferation and clonal expansion. Using two variants of a murine B-cell line that differ only in surface expression of either BCR or pre-BCR, we demonstrated that surface µHC in the pre-BCR are of the high-mannose type only, while those in the BCR are of the complex type. We further demonstrated that unlike the BCR, the high mannose pre-BCR reaches the surface as a complex with calnexin. The amount of surface μHC in the pre-B cells is lower than that in B cells. We demonstrated that µHC in pre-B cells are in large excess compared to SLC. While LC in B cells are produced in enough amounts to assemble with all µHC, SLC are produced in insufficient amounts, leaving most µHC unassembled and therefore degraded. Igα and Igβ in pre-B cells are not a limiting factor as well, since they are produced in excess compared to SLC. Hence, the lower amount of the pre-BCR as compared to the BCR is probably due to insufficient amounts of SLC. In all, the structural and quantitative differences between μHC in the BCR and pre-BCR may account for their distinct signaling functions.