Immune responses to an adjuvant-free native syngeneic myeloma protein (M315).
Myeloma protein 315 (M315; isotype IgA, lambda 2) is used in this report as a model to explore the immunogenicity of a syngeneic Ig under nearly physiological conditions. We have previously shown that a synthetic peptide spanning the mutated HV3 loop of the L-315 chain, when emulsified in complete Freund's adjuvant, elicits T helper cells (Th) that respond to a boost with L-315 or M315, indicating that M315 is recognized as a processed protein antigen. We now show that the adjuvant-free 7S monomer of native or of mildly reduced and alkylated M315, given in divided doses totalling 300 or 800 micrograms to BALB/c mice, induced persistent anti-M315 antibodies (Ab), a large part of which was IgG1 directed mainly to idiotypes (Id) associated with M315's hapten-binding site. Polymers of M315 IgA (800 micrograms) failed to induce Ab, due probably to their rapid clearance into bile. Short-term treatment with anti-CD4 monoclonal Ab GK1.5 at the time of priming with 7S M315 inhibited the responses almost completely. The spleens of M315-immune mice contained Th that recognized the L-chain subunit of M315 as a carrier indicating that these Th did not require an assembled (VH-VL) pair of 315 V regions to be activated. We also observed low amounts of Ab specific for epitopes of the C alpha region. This evidence opens the possibility that a distinct autoimmune pathway exists for elicitation of rheumatoid factor (RF; autoAb to Fc gamma) that involves help to RF-producing B cells by Id-specific Th. We suggest that these Th recognize V-region peptides from IgG that have been captured, processed and presented by these B cells.
Kristoffersen
G
G
Institute of Medical Biology, University of Tromsø, School of Medicine, Norway.
Hannestad
K
K
D000276:Adjuvants, Immunologic / Q000276:immunology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D003429:Cross Reactions; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009194:Myeloma Proteins / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins