Cross-Stimulation of Monoclonal Antibodies in Anamnestic Responses

Abstract

Immunization of BALB/c mice with Group A streptococcal vaccines leads to the induction of high levels of monoclonal antibody populations. Subsequent immunization of these mice with Group A-variant streptococcal vaccines induces a significant level of monoclonal antibody of A-variant antigen specificity revealed by labeled group A-variant polysaccharide. During these course Av and Av' immunizations, the monoclonal Group A-specific antibodies were also restimulated to levels usually higher than the variant-specific antibodies. With two exceptions, these homogeneous antibody populations were not cross-reactive in vitro with the related antigen. Such cross-stimulation of monoclonal antibodies was interpreted as a function of particular membrane properties of the Ig receptor-bearing memory cells which, for restimulation, would only require the structurally closely related antigen which serves as a backbone to the original antigen, and not necessarily the exact fit of the homologous immunodominant group.

Antibody Responses to Antigenic Determinants of Influenza Virus Hemagglutinin

“…This observation conflicts with the report of Fazekas de Saint-Groth and Webster (2, 3) that every antibody produced after a sequential immunization with cross-reacting strains of influenza A virus was cross-reactive and capable of being absorbed by both strains of virus. However, results very similar to ours have been found with different cross-reactive antigens, such as serum albumins (4), HL-A antigens (5), cross-reacting haptens (6, 7), and streptococcal antigens (8). This "aberrant" antibody recall directed against the specific determinants of the first of two related sequential antigens appears to be a characteristic of the OAS phenomenon.…”

“…This phenomenon is now well documented with many viral and nonviral cross-reacting antigens (4)(5)(6)(7)(8). However, its study with influenza antigens is of special interest because of its wide implications in the sero-epidemiology of influenza and the response to vaccination.…”

Specific and Cross-Reactive Activation of Rabbit Peripheral Blood Lymphocytes by Streptococcal Vaccines

“…Cross-stimulation of primed rabbit PBL causes not only a reciprocal in duction of PFC ( fig. 1) recognizing one or the other antigen, it fully sup ports the observations reported with the mouse model where cross-stimu lation was characterized by an identical set of clonotypes [10]. As shown in this report cross-stimulatory events are also demonstrable by measuring proliferation of lymphocytes.…”

“…There is, however, also evidence for degeneracy of antibody responses [3,10,[15][16][17]27], BALB/c mice, when immunized first with strepto coccal vaccines of the junior antigen A-CHO and 6 months later with streptococcal vaccines containing the senior antigen Av-CHO, expressed antigen-specific, hapten-inhibitable clonotypes after challenge with the homologous junior as well as the heterologous senior antigen [10]. On the basis of these observations a network of antigens was suggested to exert a profound influence on any but virgin state of immune responsive ness controlling the hierarchy of clone expression in anamnestic responses Discussion [3], The data reported in this paper argue strongly that cross-recognition at the receptor-determinant level is a basic element in immune induction.…”

The B Cell Specificity Repertoire: Its Relationship to Definable Subpopulations

“…Furthermore, the average association constant of secondary monofocal antibodies is 5fold higher than that of primary monofocal antibodies (Table II). (d) The stimulation of neonatal and primary precursor cells is exquisitely specific, whereas secondary precursor cells show a 30 per cent overlap of stimulation by cross-reactive determinants , Klinman & Press 1975b, Cramer & Braun 1973) (see Section D).…”