In vitro analysis of humoral immunity in antibody deficiency with normal immunoglobulins

The nature of the humoral immune defects in two unrelated patients with normal serum immunoglobulin and specific antibody deficiency was investigated. Five days after a booster immunization with soluble tetanus toxoid, peripheral blood lymphocyte B cells were assayed for the normal appearance of PWM and T-cell-independent antigen-specific IgG anti-tetanus lymphoblastoid B cells and suppressor T cells for these B cells. Patient 2 was totally unable to generate these B cells while patient 1 generated 10% of the normal tetanus specific B-cell activity. PBL samples were analyzed 21 days after immunization for PWM-dependent B-lymphocyte synthesis of total and anti-tetanus IgG and IgM and total and antigen-specific T-helper and -suppressor lymphocyte activity. Patient 1's B lymphocytes could generate normal amounts of both total and anti-tetanus IgG and IgM. However, his T lymphocytes completely suppressed IgG and anti-tetanus IgG production. Patient 2 also had excess radiation-sensitive T-suppressor cells for total and anti-tetanus IgG and IgM. However, this patient's B cells demonstrated an antigen-specific defect in culture in that they produced total IgG normally but were unable to produce specific anti-tetanus IgG. Thus, even with this small patient sample, the heterogeneity of immune defects established in other humoral deficiency diseases appears to exist in the syndrome of antibody deficiency with normal serum immunoglobulin.