Three distinct stages of B-cell defects in common varied immunodeficiency.

Abstract

B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig .mu. chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into 3 approximately equal groups based on their responses. The 1st group showed normal proliferation in response to the 2 B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the 2nd group showed proliferative responses to Cowan I or anti-.mu., but no differentiation to Ig-secreting cells. The 3rd group had no B-cell proliferative responses or differentiation in the assays. In several patients from each group, helper T cells were functional in Ig-secreting-cell responses with purified normal B cells; patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture; and removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. Primary B-cell defects in common varied immunodeficiency evidently occur at several levels, probably representing blocks at different stages of differentiation.