The initiation of B cell clonal expansion occurs independently of pre-B cell receptor formation

J Immunol. 2001 Nov 1;167(9):5136-42. doi: 10.4049/jimmunol.167.9.5136.

Abstract

Current models of B cell development posit that clonal expansion occurs as a direct result of Ig H chain expression. To test this hypothesis, we isolated a population of early B cells in which H chain recombination is initiated and assessed V(H)DJ(H) rearrangements in both cycling and noncycling cells. We found that actively dividing cells within this population are enriched for H chain rearrangements that are productive when compared with their counterparts in G(0)/G(1), apparently supporting a role for H chain expression in initiating early B cell division; entrance into the cell cycle was accompanied by V(H) gene-dependent H chain selection. However, we also identified a phenotypically identical population of actively cycling early B cells in the absence of H chain expression in recombination activating gene knockout mice. In addition, actively cycling early B cells could be detected in pre-B cell receptor (pBCR)-negative lambda5 knockout mice, but we found no evidence for V(H)-dependent H chain selection in this population. Given these results, we suggest that the initiation of clonal expansion, at this early stage in B cell development, occurs independently of H chain expression. Although the cycling cell pool is enriched for pBCR-positive cells in mice expressing surrogate L chain, pBCR formation is not required for the initiation of cell division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Gene Rearrangement
  • Immunoglobulin Heavy Chains / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protein Precursors / biosynthesis*
  • Receptors, Antigen, B-Cell / biosynthesis*
  • Recombination, Genetic / genetics

Substances

  • Immunoglobulin Heavy Chains
  • Protein Precursors
  • Receptors, Antigen, B-Cell