Kinetics of delayed-type hypersensitivity (DTH) reactions and Ig levels in FCA-induced dysgammaglobulinemic B 12 chickens.

Kinetic studies on delayed-type hypersensitivity (DTH) to Freund's complete adjuvant (FCA) have been done in spontaneous dysgammaglobulinemic chickens, which have drastically reduced serum IgG levels and highly elevated IgM and IgA levels - in comparison to chickens with normal immunoglobulin (Ig) levels. For a period of five weeks, serum Ig levels, leukocyte migration inhibition (LMIT), and wattle reaction were examined once a week. In normal chickens, FCA treatment resulted in stimulation of IgG, but did not affect IgM synthesis, whereas in spontaneous dysgammaglobulinemic chickens, FCA stimulated only IgM synthesis. Spontaneous dysgammaglobulinemic chickens could produce LMIT and wattle reactions as well as normal birds. Whereas in normal birds, both types of DTH reactions declined continuously about the third or fourth week, in immunodeficient chickens, further increments of LMIT and wattle reactions up to the fifth week persisted as evidenced by LMIT and wattle reactions even 15 weeks after sensitization. In contrast, only minimal signs of reactivity were seen in normal birds. Spontaneous dysgammaglobulinemic chickens, nearly unable to synthesize IgG even after FCA stimulation in vivo, lack suppressive mechanisms regulating the course of DTH reaction to FCA. The possible B-cell nature of the regulatory cell population is discussed.

Attempts to localize the defect in dysgammaglobulinemia of UM-B19 chickens by studying the effect of immunomodulating substances on immunoglobulin and antibody production.

The extreme decreased levels of IgG in dysgammaglobulinemic UM-B19 chickens are linked with decreased antibody activity. Antibody activity to T-dependent (although diminished) and T-independent antigens is present but is restricted to IgM and IgA antibodies. Complete Freund's adjuvant enhances the existing isotype pattern of serum immunoglobulins and antibodies. The antibody response to a "T-independent" antigen (B. abortus) is greatly increased by CFA in dysgammaglobulinemic chickens. Beside the appearance of high levels of IgG in dysgammaglobulinemic chickens during the first weeks of life and in transitory dysgammaglobulinemia, remarkable IgG synthesis can be temporarily induced by the mitogenic activity of LPS and even more by the regulatory function of Levamisole. Furthermore, LPS and Levamisole induce IgG antibody synthesis to concomitantly administered antigen, the IgG antibodies appearing within the normal time. Contrary to a missing feedback inhibition from total IgG to IgM serum immunoglobulins, a feedback inhibition from IgG to IgM antibodies is found. No correlation can be found between Levamisole-induced IgG immunoglobulin concentrations, and IgG antibodies. Germfree rearing for one week or longer prevents the dysgammaglobulinemic defect. The following conclusions are drawn: Early antigenic stimulation seems to be the inducing factor for dysgammaglobulinemia in UM-B19 chickens. A BG cell pool is still present in adult dysgammaglobulinemic chickens. This BG cell pool is probably diminished to a varying extent. T cell helper functions seem to be present (albeit they may be disturbed) and can be stimulated. IgG specific T cell suppression is probable. From these conclusions the etiology of the dysgammaglobulinemia in UM-B19 chickens is hypothesized to be primarily due to delayed bursal development: Immature BG cells are eliminated by environmental antigens during the neonatal period in a process similar to tolerance induction. This event, in turn, induces suppressor mechanism(s) or disturbance in helper mechanism(s).