Igg+, CD5+ human chronic lymphocytic leukemia b cells. Production of igg antibodies that exhibit diminished autoreactivity and igg subclass skewing

Mariko Wakai, Shiori Hashimoto, Masako Omata, Zev M. Sthoeger, Steven L. Allen, Stuart M. Lichtman, Philip Schulman, Vincent P. Vinciguerra, Betty Diamond, Mariella Dono, Manlio Ferrarini, Nicholas Chiorazzi

Research output: Contribution to journalArticlepeer-review

Abstract

Several questions exist regarding CD5 + B cells. These include the ability of these cells, as compared to CD5- B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects that switching may have on antigen binding. To address these issues, ten patients with chronic lymphocytic leukemia (CLL) whose CD5+ leukemic B cell clones produced IgG were studied. Monoclonal IgG was collected from PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreactivity, and DNA idiotype expression. The monoclonal B cells from 80% of the CLL patients produced IgC1 and those from 20% produced IgG3. None produced IgG2. In contrast to the known autoreactivity of IgM-producing CD5+ CLL cells (> 50% autoreactive), none of these IgG antibodies reacted significantly with the autoantigens tested. However, three did react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules expressed a cross reactive idiotypic (CRI) marker characteristic of non-mutated κ anti-DNA antibodies, three expressed a CRI displayed primarily on mutated IgG anti-DNA antibodies. Thus, some CD5+ human B cells can undergo an isotype class switch that for these CLL cells is biased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5+ cells have diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IgG antibodies could be made auto- and poly-reactive by increasing antigen-binding valency, while others expressed idiotypic markers of mutated antibodies, certain of these CD5+ B cells probably utilize non-mutated Ig V genes coding for polyreactive antibodies, whereas others may use genes that have undergone somatic mutation and that code for more restricted specificities. Therefore, both valency and VH gene mutation may account for the diminished autoreactivity of these CD5+ B cell-derived IgG antibodies.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalAutoimmunity
Volume19
Issue number1
DOIs
Publication statusPublished - 1994

Keywords

  • Autoreactivity
  • CD5 B Cells
  • Chronic Lymphocytic Leukemia
  • Cross Reactive Idiotypes
  • IgG Subclasses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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