The biological effects of IgM hexamer formation.
The inducible B cell lymphoma, CH12, and its in vitro adapted subclone, CH12-LBK, produce immunoglobulins of identical sequence, specificity and isotype, with equivalent affinities for the hapten trimethyl ammonium. However, the hemolytic efficiencies of the antibody secreted by the two cell lines are quite different. Antibody preparations from lipopolysaccharide-stimulated CH12 cells lyse erythrocytes six- to ten times more effectively than antibody preparations of the same concentration from CH12-LBK cells. Both cell lines secrete polymeric IgM, but while CH12-LBK cells secrete predominantly the canonical pentameric IgM, CH12 cells secrete a mixture of pentamers and hexamers. High-efficiency complement-dependent cytolysis is associated with hexameric IgM, which has a specific activity that is approximately twenty times higher than that of the pentameric form. J chain protein is found in the secreted IgM of both cell lines, but is associated only with the pentameric IgM and not with the hexameric form, nor with any intermediate polymers smaller than a pentamer. A deficit in, or the inaccessibility of, J chain protein appears to facilitate hexamer formation. These experiments confirm previously published data showing that J chain is not necessary either for assembly or secretion of polymeric IgM, and suggest instead that J chain may be important in regulating the lytic efficiency of polymeric IgM by controlling the IgM pentamer/hexamer ratio. The experiments further suggest a mechanism, in addition to isotype switching and somatic mutation, by which the biological efficiency of antibodies from a single clone of B cells can be regulated.
Randall
T D
TD
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
King
L B
LB
Corley
R B
RB
D006461:Hemolysis; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000032:analysis / Q000502:physiology; D007075:Immunoglobulin M / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008223:Lymphoma / Q000276:immunology; D008854:Microscopy, Electron; D014407:Tumor Cells, Cultured
D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; C024242:polymeric IgM