Identification and analysis of a novel human surface CD5- B lymphocyte subset producing natural antibodies

Marion T. Kasaian, Hideyuki Ikematsu, Paolo Casali

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

The production of "natural" autoantibodies or antibodies, i.e., Ig that bind a variety of self- and/or exogenous Ag and arise independently of known immunization, is thought to be a feature of CD5+ B lymphocytes. To determine whether other lymphocyte subsets exist that might be committed to the production of natural antibodies, human peripheral blood B cells were sorted on the basis of surface CDS expression and differential expression of surface CD45RA (CD5+CD45RAintermediate(int), CD5- CD45RAlow(lo), and CD5-CD45RAhigh(hi)), and analyzed for the type of Ig produced after EBV infection and culture. Like their CD5+ counterparts, most CD5-CD45RAlo B lymphocytes were precursors of cells producing IgM, a major proportion of which displayed the Ag-binding features of natural antibodies. In contrast, CD5-CD45RAhi B cells comprised a high frequency of IgG-producing cell precursors, possibly including memory B lymphocytes. Six of seven IgM mAb generated from sorted CD5-CD45RAlo B cells and three of four IgM mAb from sorted CD5+ B cells were polyreactive, binding with different affinities (Kd, 10-5 to 10-8 M) to two or more Ag; the remaining mAb from CD5-CD45RAlo and the mAb from CD5+ B cells each bound to a single Ag (Kd, 10-7 to 10-8 M), β-galactosidase and ssDNA, respectively. CD5-CD45RAlo B cells account for 4.1 ± 1.2% (mean ± SD in 11 healthy subjects; CD5+ B cells, 23.3 ± 6.9%) of total B lymphocytes and display the features of quiescent cells. In a given individual, the number of CD5-CD45RAlo B cells remains constant over time. CD5-CD45RAlo and CD5+ B cells bear surface CD11b and CD14, at densities and/or frequencies apparently higher than those of CD5-CD45RAhi B lymphocytes. Despite their surface CD5- phenotype, CD45RAlo B cells express CDS mRNA at levels comparable with those of CD5+ B lymphocytes, whereas CD5-CD45RAhi B cells express only trace amounts of CDS mRNA. The commitment to natural antibody production and the degree of CDS mRNA expression suggest that the newly defined CD5-CD45RAlo B cell subset is related to CD5+ B lymphocytes, and may constitute the human homologue of the mouse Ly-1- "sister" B cell population.

Original languageEnglish (US)
Pages (from-to)2690-2702
Number of pages13
JournalJournal of Immunology
Volume148
Issue number9
StatePublished - May 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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