Activated B cells from patients with common variable immunodeficiency proliferate and synthesize

Most patients with common variable immunodeficiency (CVI) have normal numbers of circulating B cells but low concentra-tions of serum Ig. To determine if the hypogammaglobulinemia is caused by an intrinsic B cell defect, we studied B cell function of 22 CVI patients. Cultured B cells from all CVI patients un-derwent normal proliferation and synthesized normal quanti-ties of IgE in the presence of anti-CD40 and IL-4. If cultured with anti-CD40 and IL-10, four patterns of Ig isotype synthe-sis were observed. Six CVI patients produced normal amounts of IgM, IgG, and IgA. Four patients produced normal quanti-ties of IgM and IgG. Ofthe remaining 12 patients who failed to synthesize IgG and IgA, 8 produced normal and 4 synthesized decreased amounts ofIgM. Analysis ofthe IgG subclasses pro-duced by 10 patients with IgG-secreting B cells revealed that IgG4 was the most affected subclass, followed by IgG2; synthe-sis of IgG3 and IgGl remained normal. Similarly, in the six IgA producing patients, IgA2 was more often affected than IgAl. The hierarchy of Ig isotype and subclass synthesis corresponds to Ig heavy chain constant region gene location on chromosome 14. Thus, circulating B cells of CVI patients are committed to synthesize one or more Ig isotypes or subclasses, and under proper conditions can proliferate, mature into Ig-secreting cells, and undergo class switch to IgE. (J. Clin. Invest. 1993