Distinct patterns of heavy chain variable region subgroup use by human monoclonal autoantibodies of different specificity.

Abstract

In some of the earliest experiments proving the existence of crossreactive idiotypes (CRIs), Kunkel et al. (1) CRIs associated with the L and H chains ofCAs have also been described (reviewed in reference 4) . Many CAs bind to the I antigen, a developmentally regulated carbohydrate moiety on the erythrocyte membrane (5) . The CAs with anti-I specificity generally use VkIII L chains, which may also derive from the Humkv325 gene and/or closely related genes (2, 6). As both RFs and CAs frequently use the same Humkv325-derived L chains, we reasoned that the two types of autoantibodies should display quite distinct patterns of H chain use . To test this hypothesis, we used synthetic peptides to generate primary sequence-dependent antibodies specific for the three major human VH protein subgroups (7) . Initial studies of RFs from unrelated individuals revealed that Humkv325-derived antibodies often express anti-IgG activity when paired with a subset of VHI H chains (7) . In marked contrast, the present results

Normal B Cells Express51p1-Encoded Ig Heavy Chains That Are Distinct From Those Expressed by Chronic Lymphocytic Leukemia B Cells

“…CLL B cells have been shown to express IgM Abs that display reactivity to self-proteins. In addition, several 51p1-encoded Ig expressed in CLL are polyreactive, having reactivity to IgG, cardiolipin, DNA, actin, and thyroglobulin (35)(36)(37)(38)(39)(40). Such polyreactivity is characteristic of some "natural" autoantibodies produced early in B cell development.…”

Structural characterization of the second major cross‐reactive idiotype group of human rheumatoid factors. Association with the VH4 Gene Family

“…1). We have recently demonstrated that the great majority of d I I b RF (77%) use VHl-deriVed heavy chains (3). These H chains bear a CRI identified by MAb G6 (43).…”

Transgenic Expression of a Human Polyreactive Ig Expressed in Chronic Lymphocytic Leukemia Generates Memory-Type B Cells That Respond to Nonspecific Immune Activation

“…CLL B cells have been shown to express IgM Abs that display reactivity to self-proteins (27,61,62). In addition to SMI, several other 51p1-encoded Ig expressed in CLL are polyreactive, having reactivity to IgG, cardiolipin, DNA, actin, and thyroglobulin (23,(63)(64)(65)(66)(67). Several studies have postulated that CLL may arise from a clonal outgrowth of B cells (68,69), based on identification of the restricted use of certain D segments and J H genes in 51p1-encoded Ig expressed by CLL B cells encode a third complementarity determining region with conserved amino acid motifs (69).…”