Defective antigen presentation by macrophages from mice genetically selected for low antibody response

Abstract

Rome Mice, selected for high (H) and low (L) antibody responses to xenogeneic erythrocytes (Biozzi mice, selection I), have been tested for their immune responsiveness to lysozymes. The anti-ring-necked pheasant egg-white lysozyme (REL) and anti-hen egg-white lysozyme (HEL) primary plaque-forming cell responses are 20 to 40-fold lower in L than in H mice. The heterogeneity of anti-HEL antibodies in the secondary response, as analyzed by isoelectric focusing, is highly reduced in L as compared to H mice. The in vitro anti-HEL plaque-forming cell secondary response of (H X L)Fl lymph node (LN) cells is induced by HEL-pulsed macrophages (M@) from H, but not from L, mice. Therefore, genetic differences affecting antibody responsiveness in H and L mice are expressed at the level of antigen-presenting cells. This genetic defect observed in L cells has been studied in more detail using an antigen-specific, T celldependent LN cell proliferative assay. After HEL-complete Freund's adjuvant (CFA) priming, LN cells from H or (H X L)Fl mice respond to HEL, REL (which is cross-reactive with HEL) and purified protein derivative of tuberculin (PPD), whereas LN cells from L mice do not respond to HEL or REL but proliferate in the presence of PPD. Proliferation of HEL-CFA primed (H X L)F1 LN cells is induced by HEL-or REL-pulsed M@ from H but not from L mice, whereas PPD-pulsed M@ from H or L mice give similar proliferative responses. By increasing %-fold the concentration of HEL used to pulse M@ from H and L mice, a comparable proliferative response is obtained when HEL-CFA-primed (H X L)Fl LN cells are stimulated with HEL-pulsed M@ from either line. This finding indicates that the genetic defect at the antigen-presenting cell level in L mice is not absolute, but rather reflects a different antigen handling by M@ in the two lines.

Processing and presentation of ovalbumin in mice genetically selected for antibody response

“…3, B.lO.S and L-I M a did not differ in their ability to stimulate eight distinct T-T hybridomas in the presence of OVA. Our results differ from those of Adorini and Doria [7],who noted a difference in the capacity of HEL-pulsed M a of the H-I and L-I mice to stimulate HEL-primed F1 T cells.The H-25 haplotype of the L-I line, well known to be a low H-2 responder haplotype to HEL [lo], may explain this finding. Furthermore, in F1 mice there is a dominance of the response to the preferred haplotype (another Ir gene effect).…”

“…Wiener and Bandieri [6] reported a significant difference in the retention of membrane-bound 12sII-KLH between the MQ from the H-I and L-I lines. Subsequently, Adorini and Doria [7] observed that hen egg lysozyme (HEL)-pulsed M@ from H-I mice were much more effective in stimulating HEL-primed F1 T cells than HEL-pulsed M@ from L-I mice. Both groups concluded that the difference in Ab responsiveness between the H-I and L-I lines could be explained at least in part by differences in Ag processing between the M@ of these two lines of mice.…”

Functional Differences in the Specific B‐Cell Compartment in High or Low Antibody Responder Mice

“…This question has been further reconsidered in terms of Ag processing and presentation. Adorini & Doria [8] observed that Ag pulsed macrophages from HI were more effective than those of LI mice in stimulating primed (HI 2 LI) F1 T cells. However, the difference in I-A restriction between HI (H-2 q ) and LI (H-2 s ) may impair the significance of these results.…”

Immune Response to the Rhodococcus equi Infection in High and Low Antibody‐Producing Mice (Selection IV‐A)

“…These two lines gave identical antibody responses to the somatic antigen of Salmonella used in Selection IV. Several studies have demonstrated that the selective breeding modifies macrophage function in an opposite direction to that of antibody production for Selections I, II and IV-A (1,5,7,17,21). Macrophages of L mice presented high catabolism of the immunogens with consequent deficiency in their antigen presentation function leading to a low antibody production.…”