Epitope‐specific regulation. III. Induction of allotype‐restricted suppression for IgG antibody responses to individual epitopes on complex antigens

摘要

AbstractMaternal antibody to the paternal Igh‐1b (IgG2a) allotype induces chronic suppression for Igh‐1b (1b) production in (BALB/c × SJL)F1hybrid mice. These mice characteristically remain incapable of producing lb antibody responses until about 3 months of age and then enter a remission phase during which they produce normal 1b antibody responses to antigens introduced initially at this time. Thus young allotype‐suppressed mice do not produce lb antibody responses to dinitrophenylated keyhole limpet hemocyanin (DNP‐KLH) and 1b anti‐ KLH.The suppression of 1b antibody responses in young allotype‐suppressed mice prevents the expression, rather than the development, of 1b memory for priming antigen epitopes. Furthermore, it not only prevents the expression of such memory cells initially but results in the induction of a continued suppression that specifically prevents their expression after the onset of remission. Thus mice primed with DNP‐KLH while allotype suppression is still active develop normal 1b memory for DNP and KLH but nonetheless fail to produce lb anti‐DNP and 1b anti‐KLH responses, even when restimulated with DNP‐KLH during remission. These mice also fail to produce 1b anti‐DNP when stimulated with DNP on an unrelated carrier molecule,i.e., with DNP‐chicken gamma globulin (CGG).This suppression is both epitope‐specific and allotype‐specific. That is, although 1b responses to DNP on CGG are suppressed, 1b responses to CGG epitopes on DNP‐CGG proceed normally. Furthermore, there is no suppression of other isotype and allotype responses either to DNP or to the CGG epitopes. These data therefore define an Igh‐restricted epitope‐specific mechanism that can be induced to persistently suppress 1b antibody responses to epitopes introduced initially durin