Identification of anergic B cells within a wild-type repertoire

Immunity. 2006 Dec;25(6):953-62. doi: 10.1016/j.immuni.2006.10.017.


The contribution of anergy to silencing of autoreactive B cells in physiologic settings is unknown. By comparing anergic and nonanergic immunoglobulin-transgenic mouse strains, we defined a set of surface markers that were used for presumptive identification of an anergic B cell cohort within a normal repertoire. Like anergic transgenic B cells, these physiologic anergic cells exhibited high basal intracellular free calcium and did not mobilize calcium, initiate tyrosine phosphorylation, proliferate, upregulate activation markers, or mount an immune response upon antigen-receptor stimulation. Autoreactive B cells were overrepresented in this cohort. On the basis of the frequency and lifespan of these cells, it appears that as many as 50% of newly produced B cells are destined to become anergic. In conclusion, our findings indicate that anergy is probably the primary mechanism by which autoreactive B cells are silenced. Thus maintenance of the unresponsiveness of anergic cells is critical for prevention of autoimmunity.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Clonal Anergy / immunology*
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Complement / immunology
  • Receptors, Complement / metabolism
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism
  • Self Tolerance / immunology*


  • Membrane Glycoproteins
  • Receptors, Antigen, B-Cell
  • Receptors, Complement
  • Receptors, IgE
  • complement 1q receptor