Clonal anergy: the universally anergic B lymphocyte

Proc Natl Acad Sci U S A. 1982 Mar;79(6):2013-7. doi: 10.1073/pnas.79.6.2013.

Abstract

The clonal anergy theory of induction of immunological tolerance states that differentiating B lymphocytes that encounter multivalent antigen at the pre-B to B cell transition stage can receive and store a negative signal, which renders them anergic to later triggering stimuli. The theory was tested by using an anti-mu chain monoclonal antibody, E4, as a model tolerogen. The fluorescence-activated cell sorter was used to select B cell-free cell populations from adult murine bone marrow or newborn spleen, and later, to analyze B cell neogenesis in vitro. The presence of E4 at greater than or equal to 1 microgram/ml was required to impede the development of normal numbers of B cells with full receptor status. The subsequent capacity of these B cells to respond in vitro to mitogens was assessed in a filter-cell free microculture system that allows single B cells to proliferate and differentiate. Concentrations of E4 far below those required to affect B cell neogenesis had profound inhibitory effects on the subsequent functional capacity of the B cells. In fact, 10(-3) micrograms/ml of E4 markedly impaired both proliferation and antibody formation, and 10(-1) micrograms/ml, which had no effect on Ig receptor development, abrogated functional capacity. Thus B cells formed in the presence of E4 at 10(-1) micrograms/ml, though possessing the receptor status typical of B cells, were functionally entirely anergic. Exposure to E4 appeared to accelerate the spontaneous death rate of newly formed B cells in vitro. Whether the anergic cell would also have a shortened life span in vivo is not known.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic
  • Antibody Formation
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Division
  • Cell Survival
  • Clone Cells / immunology
  • Immune Tolerance*
  • Immunoglobulin mu-Chains / immunology
  • Mice
  • Receptors, Antigen, B-Cell / immunology*

Substances

  • Antibodies, Anti-Idiotypic
  • Immunoglobulin mu-Chains
  • Receptors, Antigen, B-Cell