Modulation of regulatory mechanisms operative in the cyclical production of antibody.

Abstract

Modulation of the cyclical response in rabbits to aggregated human gamma globulin (AHuIgG) was investigated in order to study some of the parameters involved in self-regulation of the immune response. Several mitogens (lipopolysaccharide [LPS], phytohemagglutinin [PHA], and concanavalin A [Con A]), when injected simultaneously with antigen, have been shown to modulate the normal splenic plaque-forming cell (PFC) response in rabbits to a single intravenous injection of AHuIgG. This response to AHuIgG has previously been characterized by the initial appearance of PFC in the spleen 3 days later, with a peak of PFC at 5 days after injection. The number of PFC in the spleen then decreases and remains at a low level until a second increase begins on day 10, peaking on day 13. The 8-day cycle between peak PFC repeats, with a third peak appearing on day 21. In the present studies, injection of LPS with AHuIgG was shown to affect the PFC response by enhancing only the initial peak of PFC, PHA was shown to enhance both the initial and secondary peaks of PFC, while injection of Con A with AHuIgG resulted in a prolonged increase in PFC with no apparent cycling. Irradiation 24 h after injection of antigen resulted in PFC kinetics similar to those observed with PHA, although the increase in PFC was more marked with irradiation. Thus, although LPS, PHA, Con A, and irradiation markedly affected the immune response to AHuIgG, Con A was the only substance which altered the cyclical appearance of PFC to HuIgG. The cyclical nature of the PFC kinetics was shown to occur with either intravenous or intraperitoneal injection of antigen and in both primary and secondary responses, provided that the rabbits were primed with a low dose of antigen. Data were obtained that suggest that the response in distal lymph nodes may be regulated by immunological events occurring in the spleen. Cycling of PFC was not observed in the draining node after subcutaneous injection of AHuIgG in the hind foot. However, if the antigen was also injected intravenously at the same time as the subcutaneous injection, the response in the node became cyclical.

Thymic requirement for cyclical idiotypic and reciprocal anti-idiotypic immune responses to a T-independent antigen.

“…Cycling has been noted in various species with antigens ranging from haptens (16) to bacterial antigen (2) and alloantigens (17), and in both T-independent and Tdependent antibody responses (2)(3)(4)(5)(6)(7)(8), as well as cell-mediated responses (18,19). The cycling is independent of the immunization route and of the serum antibody levels (1)(2)(3)(4)(5)(6)(7)(8). What is most remarkable is that the peaks of AFC appear almost exactly every 6-10 d regardless of the antigen or animal species.…”

Detection of immune complexes. The use of radioimmunoassays with Clq and monoclonal rheumatoid factor.

“…The possible role of immune complexes in a variety of basic immune mechanisms is currently under intensive study (1)(2)(3)(4) and in addition immune complexes have been shown to have an important role in a wide variety of diseases (5)(6)(7)(8)(9)(10)(11)(12). 1 Various techniques have been described for detecting immune complexes (13,14) but none so far have achieved the sensitivity, quantitative capacity, and simplicity for wide application. A major approach to the detection of immune complexes has been the use of reagents which will react preferentially with complexed immunoglobulins but not monomeric immunoglobulins.…”

Oscillations in the immune system

“…Cyclical patterns to antigen challenge in both the antibody response and the cell‐mediated immunity have been described for over 40 years (124). Particularly, clear experimental time‐courses showing two or three peaks in B‐cell populations have been presented (125, 126).…”

“…Because experimental data were only collected for 2 or 3 weeks, it is difficult to determine whether such oscillations continue. Typically such results were described as a bi‐phasic B‐cell response to antigen (124, 126, 127), but one of the subjects (125) clearly shows a strong third peak, whereas other data (126) suggest a small third peak that might indicate a decaying oscillation. Such oscillations were usually interpreted as being caused by regulatory mechanisms within the immune system, although specific mechanisms have never been described.…”