Cross-reactive idiotypic

CRI Cross-reactive idiotype CRPC- reactive protein eSA Cyclosporin A CSF Colony-stimulating factor... 

Inghirami, G., Foitl, D. R., Sabichi, A., Zhu, B. Y., and Knowles, D. M., Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes Distribution and characterization, including Ig VH gene and CD5 antigen expression. Blood 78,1503-1515 (1991). 

Guery JC, Druet E, Glotz D, Hirsch F, Mandet C, De Heer E,and Druet P. Specificity and cross-reactive idiotypes of anti-glomerular basement membrane autoantibodies in HgCl2-induced autoimmune glomerulonephritis. European Journal of Immunology 20 93-100,1990. 

Feizi et al. (1977) have described a heavy-chain variable region marker (VnMar) that was detected using an antiserum raised against human IgM cold agglutinins. Evidence was presented that the relevant determinant was associable with cross-reactive idiotypes characteristic of the cold agglutinins. It was of particular interest that this antigen is found in both normal pooled IgG and some unselected myeloma paraproteins. 

In Fi (A/J X BALB/c or A/J X C57BL/6J) mice, about 9 out of 10 animals immunized with KLH-Ar produced the cross-reactive idiotype (62). This indicates that the absence of the idiotypic marker in BALB/c or C57BL antibodies is not due to the presence of a dominant gene which suppresses its expression Fi mice would carry this gene and lack the idiotype. 

Immunological memory, for the production of the cross-reactive idiotype, can also be suppressed after primary immunization with the phenylarsonate-protein conjugate (104a). This observation indicates that memory cells are subject to inactivation by heterologous antiidiotype antibodies and, also, that they are accessible in vivo. 

For three other myeloma proteins having anti-(l — 6)-a-D-glucopyranan specificity (W 3129, W 3434, and QUPC 52), the authors found a somewhat different pattern of cross-reactivity.63 The reaction of W 3129 with its anti-idiotypic antibody was not totally inhibitable by even high concentrations of W 3434 protein, and not at all by protein QUPC 52. Thus, proteins W 3129 and W 3434 share some determinants, but are clearly different from each other and from QUPC 52. 

F6. Fong, S., Gilbertson, T. A., Chen, P. P., Vaughan, J. H., and Carson, D. A., Modulation of human rheumatoid factor-specific lymphocyte responses with a cross-reactive anti-idiotype bearing the internal image of antigen. J. Immunol. 132, 1183-1189 (1984). 

It would be of extreme interest to determine whether any interspecies idiotypic cross-reactions could be observed. Could there be, for example, a cross-reaction between idiotypic determinants on an antibody of given specificity (say, antidinitrophenol) produced in a second species. To the authors knowledge, no reports of such cross-reactivity have yet appeared. However, the basic unity observed in the construction of the antibody-combining-site structure, at least among mammalian species, would suggest that such interspecies cross-reactivity is a very real theoretical possibility. 

These results, together with data on idiotypic specificities in inbred mice, indicate that idiotype can be transmitted genetically. It should be noted, however, that studies of rabbit antiproteus (7), antisalmonella (8) and antipneumococcal (40c) antibodies have not revealed any pattern of cross-reactivity within a family. Why rabbits producing high titers of antistreptococcal antibodies tend to produce antibodies with shared idiotype remains to be elucidated. A similar question arises with respect to inbred mice the occurrence of strong intrastrain idiotypic cross-reactions varies with the antigen and the strain. 

Another example of idiotypic cross-reactivity between myeloma proteins and induced antibodies was reported by Weigert and his collaborators (54,55). They found that a small but significant percentage of myeloma proteins induced in BALB/c mice have antibody activity against a(l 3)dextran and share idiotypic specificity. These include an IgM as well as a number of IgA proteins all are of type X. The same idiotypic specificity was found in anti-a(l 3)dextran antibodies of all immunized, normal BALB/c mice. 

The suppressed mice produced anti-Ar antibodies in titers comparable to those of controls. Interestingly, the idiotypic specificities of the anti-Ar antibodies arising in different, suppressed A/J mice were not cross-reactive with one another (104). This result indicates that A/J mice are capable of synthesizing a large variety of antibody molecules specific for the azophenylarsonate group but that expansion of one or a few identical clones occurs in all nonsuppressed mice of that strain. 

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