Association of the pre-B cell receptor (BCR) expression level with the quality of pre-BII cell differentiation reveals hierarchical pre-BCR function

Mol Immunol. 2007 Mar;44(7):1765-74. doi: 10.1016/j.molimm.2006.07.301. Epub 2006 Sep 27.

Abstract

The expression of a pre-B cell receptor (pre-BCR) is required for allelic exclusion and pre-BII cell differentiation. V(H)12 microH chains are unusual in that they form pre-BCRs and mediate allelic exclusion, but most cannot drive pre-BII cell differentiation. To explain this paradox, we examined pre-BCR functions and pre-BII cell differentiation in mice expressing microH chain transgenes encoding a B cell-permissible V(H)12 microH chain (designated 10/G4(6-1)), and a non-permissible V(H)12 microH chain (designated 8/G0). Compared with 10/G4 pre-BCRs, 8/G0 pre-BCRs are expressed at low levels on the cell surface. 8/G0 pre-BCRs mediate allelic exclusion, but 8/G0 pre-BII cells are defective in proliferation and expression of survival factors Bcl-2, Bcl-X(L) and hemokinin 1 (HK1). Increasing 8/G0 microH chain production restores HK1 transcription and improves proliferation of pre-BII cells as well as later stage B cell development. These data reveal a hierarchy of pre-BCR function that determines the development and plasticity of early B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Bone Marrow / immunology
  • Cell Differentiation
  • Cell Membrane / chemistry
  • Homozygote
  • Interleukin-7 / pharmacology
  • Lymphocyte Activation* / genetics
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Pre-B Cell Receptors
  • Protein Precursors / analysis
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Antigen, B-Cell / analysis
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism*
  • Spleen / immunology
  • Tachykinins / analysis
  • Tachykinins / genetics
  • Tachykinins / metabolism
  • bcl-X Protein / analysis
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Bcl2l1 protein, mouse
  • Interleukin-7
  • Membrane Glycoproteins
  • Pre-B Cell Receptors
  • Protein Precursors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • Tac4 protein, mouse
  • Tachykinins
  • bcl-X Protein