Human immunoglobulin selection associated with class switch and possible tolerogenic origins for Cδ class-switched B cells Academic Article Article uri icon

Overview

MeSH Major

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation
  • Interleukins
  • T-Lymphocytes, Regulatory

abstract

  • Current paradigms of peripheral B cell selection suggest that autoreactive B cells are controlled by clonal deletion, anergy, and developmental arrest. We report that changes to the human antibody repertoire likely resulting from these mechanisms both for a well-characterized autoreactivity from antibodies encoded by the V(H)4-34 gene and for other hallmarks of an autoreactive repertoire are apparent mainly for class-switched B cells and not for IgM germinal center, IgM memory, or IgM plasma cells. Other possible indicators of autoreactivity found selected with immunoglobulin class include J(H)6 gene segment usage, increased frequency of B cells with long third hypervariable regions, and distal J(kappa) gene segment bias. Of particular interest is the finding that B cells with these same characteristics are selected into the lineage of B cells that have undergone the unusual class switch from constant region C mu to C delta (C delta-CS). The C delta-CS population also displays an increased frequency of charged amino acids localized to the complementarity-determining regions, further suggesting autoreactivity, and evidence is presented that these B cells had undergone extensive receptor editing. Thus, the C delta-CS lineage may be a "sink" for B cells harboring autoreactive specificities in normal humans. A model for a new tolerizing mechanism that could account for the C delta-CS lineage is presented.

publication date

  • April 2004

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1172/JCI200420255

PubMed ID

  • 15085198

Additional Document Info

start page

  • 1188

end page

  • 201

volume

  • 113

number

  • 8