Activated B cells express increased levels of costimulatory molecules in young autoimmune NZB and (NZB x NZW)F(1) mice

Clin Immunol. 2000 Jan;94(1):51-63. doi: 10.1006/clim.1999.4806.

Abstract

Polyclonal B cell activation is a hallmark of autoimmune disease in NZB and (NZB x NZW)F(1) (NZB/W) mice. However, the mechanism by which this activated cell subset facilitates disease development is unknown. We recently showed that resting B cells from these mice demonstrate enhanced expression of costimulatory molecules in response to CD40 crosslinking (Jongstra-Bilen et al., J. Immunol. 159,5810-5820, 1997). This led us to question whether activated B cells expressed costimulatory molecules in vivo. Using flow cytometry we found that NZB and NZB/W mice have an increased proportion of splenic B cells expressing B7.1 and elevated levels of B7.2 and ICAM-1. These B cells isolate within the low-density activated population and possess the phenotypic characteristics of marginal zone B cells. The levels of B7.1 on the activated B cell population are similar to those induced by CD40 stimulation raising the possibility that activated B cells in NZB and NZB/W mice provide costimulatory signals to self-reactive T cells leading to loss of tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • Antigens, Surface / genetics
  • Autoimmune Diseases / metabolism
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / immunology*
  • B7-1 Antigen / metabolism*
  • CD40 Antigens / biosynthesis
  • CD40 Ligand
  • Centrifugation, Density Gradient
  • Female
  • Ligands
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred NZB / immunology*
  • Phenotype
  • Povidone
  • Silicon Dioxide
  • Up-Regulation

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • B7-1 Antigen
  • CD40 Antigens
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand
  • Percoll
  • Silicon Dioxide
  • Povidone