Frequency of Cross - Reactive Idiotype - Positive B Cells

نویسنده

  • NOLAN H. SIGAL
چکیده

Identification of antibody populations that share variable region determinants (idiotypes) among all individuals of an inbred strain has greatly facilitated the study of mechanisms that govern specific immune responses. In almost all cases, such idiotypes constitute a major portion of the antibody response, although the degree of clonal dominance may vary with the number of immunizations or during the course of a response. The observations that (a) idiotype expression can be genetically mapped to the heavy chain variable region (VH) 1 (1), (b) DNA sequences for these specificities can be isolated from a sperm genomic library (2), and (c) restriction enzyme patterns of VH correlate with idiotype and allotype inheritance (3) suggest that at least one mechanism of clonal dominance is due to the fact that these clonotypes are the direct expression of germ line genetic information. It is likely that additional mechanisms are involved in this process for several reasons. First, many inherited idiotypes have been found to comprise large families of closely related specificities (4-9), and there can be significantly greater degree of heterogeneity in idiotype-bearing hybridoma proteins characterized than is indicated by analysis of serum idiotype (4, 5). Second, the expression of an idiotype that recurs among all individuals of an inbred strain (cross-reactive idiotype; CRI) may represent the dominant specificity in one strain but constitute a minor clonotype in another (10, 11). Third, genetic information other than that coding for immunoglobulin structural genes can influence the expressed heterogeneity of some antibody responses (11, 12) and can affect the ontogeny of clonotype development (13). Such observations suggest that there might be a discrepancy between the clonotype diversity present at the precursor cell level (potential repertoire) and what is eventually expressed at the level of the serum antibody response (expressed repertoire). One of the clearest examples of this phenomenon is in the response to phosphorylcholine (PC). The murine serum response to PC is composed almost exclusively of antibodies

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تاریخ انتشار 2003