Antigen-induced exclusion from follicles and anergy are separate and complementary processes that influence peripheral B cell fate

Immunity. 1995 Dec;3(6):691-701. doi: 10.1016/1074-7613(95)90059-4.


Anergic self-reactive B cells competing within a polyclonal B cell repertoire fail to migrate into primary follicles and die after 1-3 days residence in T cell zones. Transfer of anergic HEL-specific B cells to recipients lacking HEL autoantigen and continuous bromodeoxyuridine labeling in mixed bone marrow chimeras confirms that follicular exclusion and cell death in 1-3 days is not an intrinsic characteristic of anergic cells but results from competition with B cells bearing other specificities together with continued binding of autoantigen. When naive (nontolerant) HEL-specific B cells were transferred into mice expressing HEL autoantigen, they were also excluded from follicles and their lifespan was dramatically shortened, although they became activated to express CD86 (B7-2/B70). In the presence of helper T cells, activated B cells but not anergic B cells were rescued from death and formed large extrafollicular foci to autoantibody-secreting cells. Antigen-induced exclusion from follicles is therefore an independent process from anergy that prevents self-reactive B cells from recirculating in the long-lived repertoire and may foster interactions with T cells during immune responses. By contrast, anergy prevents self-reactive B cells from collaborating with helper T cells and secreting autoantibody while trapped in the T zone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Autoantigens / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Death
  • Cell Movement
  • Clonal Anergy
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology*
  • Mice
  • Mice, Transgenic
  • Muramidase / immunology


  • Antibodies
  • Autoantigens
  • Muramidase