IgG subclass switch capacity is low in switched and in IgM-only, but high in IgD+IgM+, post-germinal center (CD27+) human B cells

Eur J Immunol. 2001 Jan;31(1):243-9. doi: 10.1002/1521-4141(200101)31:1<243::AID-IMMU243>3.0.CO;2-0.

Abstract

Recent studies have shown that in humans the germinal center reactions produce three types of V(D)J mutated B cells in similar proportions, i.e. Ig-switched, IgD-IgM+ (IgM-only) and IgD+IgM+ cells, and that together they form the CD27+ compartment of recirculating B cells. We investigated the Ig isotype switch capacity of these cells. Peripheral blood B subsets were sorted and IgG subclass secretion in presence or absence of IL-4 was compared in B cell assays which lead to Ig secretion in all (coculture with EL-4 thymoma cells) or only in CD27+ (CD40L stimulation) B cells. Already switched IgG+ B cells showed no significant sequential switch and IgM-only cells also had a low switch capacity, but IgD+CD27+ switched as much as IgD+CD27- B cells to all IgG subclasses. Thus, in switched B cells some alterations compromising further switch options occur frequently; IgM-only cells may result from aborted switch. However, IgD+CD27+ human B cells, extensively V(D)J mutated and "naive" regarding switch, build up a repertoire of B cells combining (1) novel cross-reactive specificities, (2) increased differentiation capacity (including after T-independent stimulation by Staphylococcus aureus Cowan I) and (3) the capacity to produce appropriate isotypes when they respond to novel pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / metabolism*
  • Germinal Center / metabolism*
  • Humans
  • Immunoglobulin Class Switching*
  • Immunoglobulin D / biosynthesis*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / classification*
  • Immunoglobulin M / biosynthesis*
  • Lymphocyte Activation
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis*

Substances

  • Immunoglobulin D
  • Immunoglobulin G
  • Immunoglobulin M
  • Tumor Necrosis Factor Receptor Superfamily, Member 7