HOW MANY SPECIFIC B-CELLS ARE NEEDED TO PROTECT AGAINST A VIRUS

The size of the Ab repertoire has been estimated to comprise theoretic ally somewhere between >10(10) and approximately 10(4) specificities, dependent on the criteria used. In an attempt to estimate the anti-vir al protective Ab repertoire of the mouse the B cell and Ab-forming cel l (AFC) frequencies and protective neutralizing Ab levels during the c ourse of an infection with vesicular stomatitis virus (VSV) were analy zed. Determination of AFC frequencies, limiting dilution assays, and a doptive transfer experiments to SCID mice revealed that during the acu te phase (day 8) of the immune response, more than 50% of all IgG2a-pr oducing AFCs were specific for VSV, most of them recognizing the neutr alizing determinant. In a later phase (days 21 or 50), 10 to 20 times fewer VSV-specific AFCs were present, corresponding to a frequency of approximately 1:10(4) Spleen cells. Finally, in a protection assay in SCID mice, adoptively transferred protective Ab concentrations were fo und to be approximately 1 to 10 mu g Ab/ml mouse serum. Because during the memory phase of the anti-VSV response usually 10(4) AFC/mouse are engaged to maintain a high level of memory IgG against the neutralizi ng determinant on VSV and if one assumes a total number of about 10(6) AFCs/mouse, these data suggest a rather limited neutralizing anti-vir al protective memory-AFC repertoire of 10(2) to 10(4) different specif icities.