Expanded population of activated antigen-engaged cells within the naive B cell compartment of patients with systemic lupus erythematosus

J Immunol. 2008 Jan 15;180(2):1276-84. doi: 10.4049/jimmunol.180.2.1276.

Abstract

Polyclonal B cell activation is a well-described feature of systemic lupus erythematosus (SLE), but the immune mechanisms leading to this activation are unclear. To gain insight into these processes, we extensively characterized the activated peripheral blood B cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various combinations of conjugated Ab to identify distinct peripheral B cell subsets, and activation was assessed by measurement of forward scatter and CD80 or CD86 expression using flow cytometry. SLE patients had altered proportions of several B cell subsets, many of which demonstrated increased activation as assessed by forward scatter. This activation occurred at an early developmental stage, as B cells in the transitional (T2) stage were already significantly larger than those seen in controls. Increased proportions of CD80- or CD86-expressing cells were also seen in multiple B cell subsets, with the most striking differences observed in the naive CD27-CD23+ population. Within the CD23+ subset, increased costimulatory molecule expression was most pronounced in an IgD+IgMlow population, suggesting that activation follows Ag engagement. Although controls also had IgD+IgMlowCD23+ cells, they were reduced in number and not activated. Thus, there is an altered response to Ig receptor engagement with self-Ags in lupus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantigens / immunology
  • B-Cell Activating Factor / blood
  • B-Lymphocyte Subsets / immunology*
  • B7-1 Antigen / analysis
  • B7-2 Antigen / analysis
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Interferon-alpha / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation* / genetics
  • Male

Substances

  • Autoantigens
  • B-Cell Activating Factor
  • B7-1 Antigen
  • B7-2 Antigen
  • Immunoglobulin G
  • Immunoglobulin M
  • Interferon-alpha