Abstract
B lymphocytes are regulated at multiple checkpoints during development of the pre- immune and immune repertoire (Goodnow 1996). Encounter of self-antigen within the bone marrow results in deletion, anergy or no effect depending on the strength of signal. In general, membrane self-antigens induce sufficient signal transduction or crosslinking of B cell receptor (BCR) to cause deletion (Nemazee et al. 1989; Hartley et al. 1991). In contrast, soluble antigens such as soluble hen lysozyme (sHEL) induce anergy (Goodnow et al. 1989). B cells expressing an immunoglobulin (Ig) transgene (tg) which bind dsDNA can lead to either deletion in the bone marrow (Chen et al. 1995) or peripheral tolerance (Erikson et al. 1991; Mandik-Nayak et al. 1997) depending on relative binding affinity. Mutations that alter BCR strength of signaling can affect negative selection and these findings support the model. For example, mice bearing targeted disruption of molecules involved in regulation of BCR signaling such as CD22, SHP-1 (Cyster et al. 1995), CD45 (Cyster et al. 1996) or Lyn (Cornall et al. 1998) have altered negative selection of self-reactive B cells in the sHEL/HEL-Ig double tg model. Alternatively, expression of an additional copy of CD 19 results in increased sensitivity to BCR signaling and reduction in the number of peripheral tg B cells (Inaoki et al. 1997). The complement system is an important factor in humoral immunity as binding of activated fragments of complement C3 to antigen not only enhances its localization to the lymphoid compartment but induces BCR signal transduction (Fearon et al. 1995; Carroll 1998a) (see review in this issue by M. Carroll).
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Carroll, M. (1999). Negative Selection of Self-reactive B Lymphocytes Involves Complement. In: Melchers, F., Potter, M. (eds) Mechanisms of B Cell Neoplasia 1998. Current Topics in Microbiology and Immunology, vol 246. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60162-0_3
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DOI: https://doi.org/10.1007/978-3-642-60162-0_3
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