HYPER-IGM IMMUNODEFICIENCY SYNDROME - INFLUENCE OF LYMPHOKINES ON INVITRO MATURATION OF PERIPHERAL B-CELLS

Peripheral B cells from six patients affected with the hyper-IgM immunodeficiency syndrome, characterized by an absence of IgG and IgA in serum with a concomitant elevated level of IgM, were analyzed for phenotypic and functional characteristics. We report that although the membrane antigenic pattern expression was characteristic of mature B cells, B cells from most patients exhibited an impairment in their in vitro response to several lymphokines, such as recombinant interleukin 2 (rIL-2) and low molecular weight B-cell growth factor (BCGF), that induce proliferation of anti-mu-activated B cells. This impairment was also found in response to a lymphokine mixture from a CD2-activated T-cell clone. The decrease in lymphokine-induced B-cell proliferation was accompanied by a low B-cell differentiation, whether patients' B cells were stimulated by the T-cell clone supernatant or rIL-2 and rIL6, lymphokines able to support differentiation of Staphylococcus aureus Cowan I (SAC)-activated B cells. In addition, none of the lymphokines tested were able to induce patients' B cells to switch from IgM-secreting cells to IgG- and IgA-secreting cells. We conclude that this syndrome is associated with a defect in lymphokine-dependent maturation of B lymphocytes, although the T- or the B-cell origin of the defect still cannot be determined.