Hyper IgM immunodeficiency. A primary dysfunction of B lymphocyte isotype switching.
Immunological evaluations (lymphocyte markers, B cell differentiation, T cell function) were performed on peripheral blood mononuclear cells from four individuals with hyper IgM immunodeficiency. Number, proportion, and proliferation of T lymphocytes and T lymphocyte subpopulations were relatively normal in affected individuals. The percentage and number of B cells expressing surface IgM and IgD were either normal or elevated in both blood and lymph nodes. However, surface IgG- and IgA-bearing B lymphocytes were completely absent. In vitro stimulation of blood lymphocytes with both T cell-dependent and T-cell independent polyclonal B cell activators resulted in normal numbers of IgM plasma cells and IgM secretion in cultures, but failed to induce any IgG- or IgA-producing cells. This failure of isotype switching was intrinsic to the B cell population and did not involve aberrant T cell help or suppression. Therefore, individuals with this disorder possess an intrinsic B cell dysfunction that is not related to abnormal T cell regulation.
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004406:Dysgammaglobulinemia / Q000276:immunology*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology*; D017098:IgA Deficiency; D017099:IgG Deficiency; D007075:Immunoglobulin M / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D010950:Plasma Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007075:Immunoglobulin M