Selection of stereotyped VH81X-{micro}H chains via pre-B cell receptor early in ontogeny and their conservation in adults by marginal zone B cells

Int Immunol. 2005 Jul;17(7):857-67. doi: 10.1093/intimm/dxh265. Epub 2005 May 20.

Abstract

The pre-B cell receptor (preBCR) plays critical roles in early B cell differentiation. It has been shown that not all muH chains are capable of pairing with surrogate light (SL) chains to form preBCR. Here, we established a novel system to differentially identify two types of early pre-B cell populations in bone marrow and fetal liver of mice, one producing SL-pairing muH chains and the other producing SL-non-pairing muH chains. The former population accounted for 80% of all the early pre-B cells in adult bone marrow, while it accounted for only 20% of those in fetal liver. Comparison of the two types of pre-B cell populations in fetal liver revealed the structural difference between SL-pairing and -non-pairing muH chains encoded by the V(H)81X segment that was most frequently utilized in fetal liver pre-B cells but rarely expressed by B cells generated in adults. PreBCR played an important role in the positive selection of V(H)81X-muH chains carrying the characteristic sequences of the complementarity-determining region 3 with little or no nibbling or N nucleotide addition, leading to their predominance in neonatal splenic B cells. These fetal-type V(H)81X-muH chains were also detected in adult spleen, but almost exclusively in marginal zone (MZ) B cells in contrast to the adult-type V(H)81X-muH chains. This strongly suggests that neonatally generated and selected B cells expressing the stereotyped V(H)81X-muH chains are maintained in the adult MZ and could function as innate-like lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Bone Marrow / immunology
  • Complementarity Determining Regions / immunology*
  • Gene Expression Regulation / immunology
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / immunology*
  • Gene Rearrangement, B-Lymphocyte, Light Chain / immunology
  • Immunoglobulin mu-Chains / immunology*
  • Liver / growth & development
  • Liver / immunology
  • Membrane Glycoproteins / immunology*
  • Mice
  • Pre-B Cell Receptors
  • Receptors, Antigen, B-Cell / immunology*
  • Spleen / cytology
  • Spleen / growth & development
  • Spleen / immunology

Substances

  • Complementarity Determining Regions
  • Immunoglobulin mu-Chains
  • Membrane Glycoproteins
  • Pre-B Cell Receptors
  • Receptors, Antigen, B-Cell