Transitional B cells lose their ability to receptor edit but retain their potential for positive and negative selection

J Immunol. 2007 Dec 1;179(11):7544-52. doi: 10.4049/jimmunol.179.11.7544.

Abstract

Ligation of B cell receptors on immature bone marrow B cells, either by an endogenous Ag or by an anti-B cell receptor Ab induces secondary V(D)J gene rearrangements, termed receptor editing. Whether the same signal induces receptor editing in transitional B cells is not clear. In this study, we examined the responses of immature and transitional B cells from V(H)12Vkappa1A Ig transgenic mice to stimulation with an anti-Igbeta Ab. Our results demonstrated that immature B cells stimulated with a low concentration of anti-Igbeta Ab, mimicking Ag stimulation, underwent receptor editing both in vivo and in vitro, as evidenced by the detection of dsDNA breaks at Jkappa recombination signal sequences, whereas transitional B cells did not. The lack of dsDNA breaks in transitional B cells contrasts with their increased expression of RAG1 and RAG2, suggesting a novel mechanism that may prevent rearrangements. Furthermore, treatment of transitional B cells with high concentrations of anti-Igbeta Abs induced apoptosis, whereas low concentrations induced differentiation. Our results support the idea that transitional B cells lose the capacity to edit, but are sensitive to positive and negative selection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Acetylation
  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antigen-Antibody Reactions
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Histones / immunology
  • Homeodomain Proteins / drug effects
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Immunoglobulin Heavy Chains / drug effects
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Lysine / immunology
  • Methylation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, B-Cell / drug effects
  • Receptors, Antigen, B-Cell / immunology*
  • Sensitivity and Specificity

Substances

  • Antibodies
  • DNA-Binding Proteins
  • Histones
  • Homeodomain Proteins
  • Immunoglobulin Heavy Chains
  • Receptors, Antigen, B-Cell
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • Lysine