Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Galα1,3Gal epitopes α1,3-galactosyltransferase-deficient mice

H. Ohdan, K. G. Swenson, H. S. Kruger Gray, Y. G. Yang, Y. Xu, A. D. Thall, M. Sykes

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94 Scopus citations


Human natural Abs against Galα1-3Galβ1-4GlcNAc (Gal) epitopes are a major barrier to xenotransplantation. Studies in this report, which use combined multiparameter flow cytometric sorting and enzyme-linked immunospot assay, demonstrate that anti-Gal IgM-producing cells are found exclusively in a small B cell subpopulation (i.e., CD21(-/low) IgM(high) B220(low) CD5- Mac-1- 493- cells) in the spleens of α1,3-galactosyltransferase-deficient mice. All IgM-producing cells were detected in a similar splenic subpopulation of α1,3-galactosyltransferase-deficient and wild-type mice. A higher frequency of B cells with anti-Gal surface IgM receptors was observed in the peritoneal cavity than in the spleen, but these did not actively secrete Abs, and showed phenotypic properties of B-1b cells (CD21(-/low) IgM(high) CD5- CD43+ Mac-1+). However, these became Mac-1- and developed anti-Gal Ab-producing activity after in vitro culture with LPS. The splenic B cells with anti-Gal receptors consisted of both Mac-1+ B-1b cells and Mac-1- B-1b-like cells. The latter comprised most anti-Gal IgM-producing cells. Our studies indicate that anti-Gal natural IgM Abs are produced by a B1b-like, Mac-1- splenic B cell population and not by plasma cells or B-1a cells. They are consistent with a model whereby B-1b cells lose Mac-1 expression upon Ag exposure and that these, rather than plasma cells, become the major IgM Ab-producing cell population.

Original languageEnglish (US)
Pages (from-to)5518-5529
Number of pages12
JournalJournal of Immunology
Issue number10
StatePublished - Nov 15 2000
Externally publishedYes


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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