A pro-B-cell stage characterized by germline Ig transcription without surrogate light chain expression

Abstract

 B-cell commitment is characterized by the expression of specific membrane proteins and the rearrangement and expression of immunoglobulin (Ig) heavy (H) and light (L) chain genes. At early stages of B-cell development, unrearranged Ig loci are transcribed, which correlates with these regions becoming accessible for Ig gene rearrangement. Some germline transcripts can be translated into protein and potentially play a role in cell signaling during B-cell development. In this report an early stage in human B-cell development is characterized using Epstein-Barr virus (EBV)-transformed cell lines from patients with a severe combined immunodeficiency (SCID). These lines were shown to produce germline constant (C) gene transcripts from the IGH and IGK loci. We demonstrate here that these cells are committed to the B-cell lineage as substantiated by expression of CD79a and CD79b. No surrogate light chain (SLC) gene transcription was detected, indicative of a very early differentiation stage. From these cell lines two types of germline IgV gene transcripts were isolated: a transcript containing the IGKV4-1 gene and a germline IGHV-1 transcript nearly identical to IGHV1/OR15-1 (HC15-1, DP-1), an orphon V _H gene on chromosome 15. Germline V _H transcripts originating from the V _H locus on chromosome 14 could not be detected. It is of interest that, apart from Ig V and C genes (non-functional), V genes that reside outside the Ig locus are a target for the transcription factors that are postulated to initiate Ig gene rearrangement early in B-cell development.