EPITOPE‐SPECIFIC REGULATION OF MEMORY B‐CELL EXPRESSION *

SUMMARY IgG antibody responses to individual epitopes on complex antigens can fail despite the presence of fully competent populations of memory B‐cells, ample carrier‐specific help and the normal production of IgG antibody responses to other epitopes on the same antigen. These response failures reveal the existence of an “epitope‐specific” regulatory system that selectively controls the expression of memory B‐cells in antibody responses to hapten‐carrier conjugates and other complex antigens. Our earlier B‐cell studies describe successive stages in memory B‐cell development and consider the potential role(s) that IgD receptors on “early” memory B‐cells play in determining in situ primary and anamnestic response characteristics. 1‐5 Our more recent work, however, shows that an Igh‐restricted regulatory system also plays a major role in defining such response characteristics. 6‐12 This previously unrecognized system, which controls memory B‐cell expression (rather than development), selectively regulates IgG antibody production to each of the individual epitopes on T‐dependent antigens such as DNP‐KLH and DNP‐CGG (the DNP hapten on keyhole limpet hemocyanin and chicken gamma globulin, respectively) We have shown that this system can be induced to specifically suppress IgG2a anti‐DNP responses to DNP‐KLH without interfering with primary or secondary antibody responses to the KLH epitopes on the same molecule. Furthermore, it can be induced to specifically suppress IgH‐1b allotype responses to all DNPKLH epitopes without interfering either with other allotype and isotype responses to DNP‐KLH or with Igh‐1b responses to other antigens in the same animal. Thus, under conditions where memory development is optimal, this highly versatile regulatory mechanism is key to determining the amount, specificity, affinity and Igh isotype/allotype representation of IgG antibody responses. Since we have recently published a full description of this Igh‐restricted “epitope‐specific” system, we have chosen to briefly outline its properties here using a somewhat extended version of the “summary slides” prepared for the meeting. Many of the findings summarized in this outline are illustrated by evidence and presented at the meeting (and included here); however, this evidence was presented to underscore the importance of epitope‐specific regulation for studies of in situ and adoptive memory responses and consequently does not fully document the findings discussed. [For such documentation, we refer the reader to our published work. 6‐12