Inhibition of offspring response to HEL-CFA by administration of anti-HEL MAB to the mother is not related to the predominant idiotype, IdXE, or specificity of the MAB.
In the neonatal suckling mouse, the antibody response to HEL-CFA can be inhibited by administration of certain anti-HEL monoclonal antibodies to the mother. The murine primary response to hen egg-white lysozyme (HEL), which can be elicited in A/J mice as early as 7 days of age, is characterized by a predominant specificity that includes the 3 N-terminal amino acids of HEL (TIP-dependence) and by a predominant idiotype, IdXE. A panel of murine IgG1 anti-HEL mAbs was administered to the suckling offspring via the mother. These mAbs were not equivalent in their effects on the offspring. Only two of six IgG1 mAbs, 2F4/2E5 (IdXE-positive, TIP-dependent) and 2D1 (IdXE-negative, TIP-independent), consistently induced suppression of the response of A/J offspring when immunized at 16-20 days of age with HEL-CFA. Suppression averaged 71% for 2F4/2E5 and 74% for 2D1 and was always statistically significant (P less than .05) when 275 micrograms mAb was administered IP to the mother within 24 hr postpartum. Since 2D1 is IdXE-negative and TIP-independent, neither of these properties appears to be crucial for suppression. Differences in transfer of the mAbs from the mother to the offspring or differences in catabolism of the mAbs in the offspring were not detected. When various characteristics of the mAbs such as affinity, idiotypy, and fine specificity were considered, there was no single factor which determined suppression. One of the two mAbs that suppressed the offspring response, 2D1, is idiotypically highly connected in the anti-HEL mAb panel. This observation suggests that idiotypic interactions in the developing neonatal repertoire with subsequent perturbation of T and B cell repertoire development may be an area for future investigation.
UCLA School of Medicine, Harbor-UCLA Medical Center, Department of Pediatrics, Torrance.
C H
CH
Song
G B
GB
Calandra
C J
CJ
Palmer
A
A
Miller
E E
EE
Sercarz
M A
MA
Keller
D000818:Animals; D000833:Animals, Suckling / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000917:Antibody Formation / Q000502:physiology*; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology*; D007112:Immunity, Maternally-Acquired; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D009113:Muramidase / Q000276:immunology*; D011247:Pregnancy
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D005620:Freund's Adjuvant; D009113:Muramidase