title: Idiotypic heterogeneity of VKIII autoantibodies to red blood cell antigens.
abstract: VKIII light (L) chains are commonly expressed by human autoantibodies with diverse binding specificities, including red blood cell antigens. To better understand the physiologic and pathologic expression of these L chain variable region genes, we have created a panel of murine monoclonal anti-idiotypic antibodies by immunization with a human lymphoblastoid B cell line that secretes an IgM VKIII autoantibody specific for the I red blood cell carbohydrate determinant. The binding specificities of these nine murine monoclonal antibodies, termed IV.1-IV.9, were evaluated against a large panel of monoclonal Ig proteins and compared to two previously well-characterized monoclonal anti-idiotypes, 6B6.6 and 17.109; these two anti-idiotypes have been shown to primarily identify VKIII rheumatoid factors derived from the kv328 (VKIIIa) and kv325 (VKIIIb) genes, respectively. In contrast, our anti-idiotypic antibodies identified (public) cross-reactive idiotypes present on many VKIII proteins that included both anti-erythrocyte and rheumatoid factor autoantibodies. Certain anti-idiotypic antibodies (IV.2 and IV.6) were restricted to VKIIIa L chains but differed from the 6B6.6 anti-idiotype by binding to a larger subset of VKIIIa proteins representing the products of at least two VKIIIa genes. One antibody of our panel (IV.5) recognized a private idiotope expressed only by the immunizing antibody. Using the panel of anti-idiotypic antibodies to evaluate erythrocyte autoantibodies with different serologic specificities, we found striking heterogeneity of L chain idiotype expression, even among known VKIII anti-i/I autoantibodies. These findings differ from the recently described structural and idiotypic conservation associated with the H chain of anti-i/I autoantibodies. From correlations of idiotypic reactivity with L chains of known sequence, it is postulated that the observed heterogeneity of L chain idiotype expression is due to differences in the genetic origin and/or somatic diversification of L chain variable region genes. Furthermore, subtle variability of L chain structure may contribute in part to the differences in fine binding specificity among anti-I and anti-i autoantibodies.
authors.affiliation: Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia 19104.
authors.forename: L C
authors.initials: LC
authors.lastname: Jefferies
authors.forename: G J
authors.initials: GJ
authors.lastname: Silverman
authors.forename: C M
authors.initials: CM
authors.lastname: Carchidi
authors.forename: L E
authors.initials: LE
authors.lastname: Silberstein
mesh_terms: D000373:Agglutinins / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D002472:Cell Transformation, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology*; D006386:Hemagglutination Tests; D006801:Humans; D015151:Immunoblotting; D007122:Immunoelectrophoresis; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D000373:Agglutinins; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains