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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Boyd, A. W. Nossal, G. J. Pike, B. L. |
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. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 6 |
Volume Number | 79 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 1982-07-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | B-Lymphocytes Immunology Immune Tolerance Receptors, Antigen, B-Cell Animals Antibodies, Anti-Idiotypic Antibody Formation Cell Differentiation Cell Division Cell Survival Clone Cells Immunoglobulin Mu-Chains Mice Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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