A small CD11b(+) human B1 cell subpopulation stimulates T cells and is expanded in lupus

J Exp Med. 2011 Dec 19;208(13):2591-8. doi: 10.1084/jem.20110978. Epub 2011 Nov 21.

Abstract

A primary function of B lymphocytes is immunoglobulin production; however, the therapeutic benefit of B cell depletion in autoimmune diseases previously thought to be T cell mediated suggests that some B cells fulfill other roles in autoimmunity. We examined the recently identified human B1 cell population for T cell stimulatory activity. We found two kinds of B1 cells that are distinguished by multiple surface markers and distinct transcriptomic profiles. In both umbilical cord and adult peripheral blood, a CD11b(+) subset constitutes ~1 out of every 8-10 B1 cells, whereas a CD11b(-) subset constitutes the remaining B1 cells. These B1 cell populations differ functionally. CD11b(-) B1 cells spontaneously secrete much more IgM than CD11b(+) B1 cells. In contrast, CD11b(+) B1 cells express more CD86, and more efficiently stimulate allogeneic CD4(+) T cell expansion, than CD11b(-) B1 cells. The frequency of these CD11b(+) B1 cells is markedly elevated in lupus patients. CD11b(+) B1 cells in lupus patients express more CD86 and have increased T cell-stimulating activity in disease. This work distinguishes a novel, T cell-interacting B1 cell population whose abundance and activity may be a reflection of, and a therapeutic target in, autoimmune disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B7-2 Antigen / biosynthesis
  • B7-2 Antigen / immunology
  • CD11b Antigen*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Female
  • Fetal Blood / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / therapy
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Transcriptome / immunology

Substances

  • B7-2 Antigen
  • CD11b Antigen
  • CD86 protein, human
  • ITGAM protein, human
  • Immunoglobulin M

Associated data

  • GEO/GSE29717