Differences in the recruitment of virgin B cells into antibody responses to thymus-dependent and thymus-independent type-2 antigens.

The bone marrow of mammals generate large numbers of B cells throughout life. Most of these have a short life span. The subject of this report is to investigate the extent to which newly formed virgin B cells can be activated by thymus-dependent (TD) and thymus-independent type 2 (TI-2) antigens carrying the hapten 2,4-dinitrophenyl. The experimental approach used chimeras made between congenic rats of different kappa immunoglobulin light chain allotype. Host (kappa la) rats were depleted of peripheral B cells by whole body irradiation but had B lymphopoietic capacity conserved by shielding the hind limbs. Their peripheral B cell pool was reconstituted by transfer of kappa lb thoracic duct lymphocytes from donors immunized previously with the TD carrier. This provides test animals where newly produced virgin B cells only express kappa la but where initially most peripheral B cells are kappa lb. The TD antigen tested was able to activated both virgin and memory B cells in the period immediately following immunization. However, long-term antibody production was attributable to repeated activation of memory B cell clones without further virgin B cell recruitment. By contrast, antibody evoked by the TI-2 antigen initially was almost exclusively due to activation of donor peripheral B cells. However, over a period following TI-2 immunization there was a progressive increase in the amount of host antibody produced with corresponding decline of the donor component of the response so that the host response was dominant by six weeks. Control experiments were conducted to show that these effects could not be explained by allotype or isotype-directed suppression. The cellular basis of these differences was investigated further by studying the rate of repopulation of different B cell compartments in these chimeras by newly formed host and mature donor B cells. The results indicate that the onset of host antibody production to the TI-2 antigen closely correlated with the appearance of host B cells in the marginal zones of the spleen, whereas good TD host anti-2,4-dinitrophenyl responses antedated the appearance of host B cells in this compartment. These results are discussed in relation to other data implicating marginal zone B cells in responses to TI-2 antigens.