LOW-MOLECULAR-WEIGHT ANTIGEN ARRAYS DELETE HIGH-AFFINITY MEMORY B-CELLS WITHOUT AFFECTING SPECIFIC T-CELL HELP

An ongoing, T-cell dependent, secondary antibody response to an epitop e can be suppressed in vivo by low molecular weight, soluble polymers, bearing multiple copies of the same epitope. This study illustrates t hat such suppressive T-cell independent antigen arrays target the epit ope-specific, high affinity, memory B cells for long-term functional e limination. Splenocytes from hyperimmune unsuppressed donors, when ado ptively transferred into irradiated recipients will readily reconstitu te a secondary anti-hapten response after antigenic challenge. No such response was observed with splenocytes transferred from hyperimmune d onors suppressed with antigen arrays. The extent of suppression depend ed on antigen array dose and duration of exposure in the donor animals . The suppressive antigen array carryover from the donors into the rec ipients was negligible and insufficient to account for the observed su ppression. B cells from hyperimmune mice producing high affinity anti- fluorescein antibodies, generated by multiple fluoresceinated ovalbumi n (FL-OVA) injections, were helped efficiently by T cells from hyperim mune donors, which were either unsuppressed or suppressed with antigen arrays. Accordingly, help from T cells, specific for the carrier prot ein remains intact after such suppression. Neither lipopolysaccharide (LPS), nor additional transferred carrier-primed T cells could reverse the unresponsiveness of adoptively transferred splenocytes from suppr essed animals. Flow cytometry showed that the number of hapten-specifi c B cells was markedly reduced after suppression. Collectively, these data show that the long term elimination of an ongoing T-cell dependen t antibody response by suppressive exogenous antigen arrays is due to the functional deletion of high affinity, antigen-specific B cells, ev en in the presence of adequate T-cell help. The long-term nature of su ch functional deletion strongly suggests physical deletion of the anti gen-specific B cell population. (C) 1997 Elsevier Science Ltd.