Truncated immunoglobulin Dμ causes incomplete developmental progression of RAG-deficient pro-B cells

Abstract

Early stages of B cell development are dependent on the expression of a pre-B cell receptor (BCR), composed of a μ heavy chain (HC) in association with surrogate light chain (SLC) proteins and the signaling molecules, Igα and Igβ. During the formation of the variable region of the μ chain by somatic gene rearrangement, a truncated form of the μ protein (called Dμ) is sometimes produced by the rearrangement of a D H segment to a J H segment using one of three reading frames (designated rf2). When a Dμ protein is formed, subsequent B cell development is blocked by down-regulation of further HC rearrangements, so that a full-length μHC cannot be formed. In this study, we demonstrate that in recombinase activating gene (RAG)-2-deficient B220 + CD43 + pro-B cells in which B lymphopoiesis has been arrested at fraction C, transgenic expression of Dμ promoted partial developmental progression to fraction C′, but was unable to mediate the pro-B to pre-B cell transition to fraction D effected by full-length μHC protein. These data suggest that the intracellular signaling pathways engaged by the Dμ pre-BCR are insufficient to facilitate the expansion and/or survival of pre-B cells, and are distinct from those engaged by the pre-BCR-containing full-length μHC.