Tolerance in differentiating B lymphocytes.

Abstract

These experiments demonstrate that the response of B lymphocytes to particulate antigen in vivo can depend on their stage of differentiation: B lymphocytes differentiating from stem cells were rendered tolerant, while mature B lymphocytes were primed under the same conditions. Lethally irradiated mice of one allotype were repopulated with 13-15 day fetal liver cells from congenic mice bearing another allotype and the effect of antigen on the emergence of responsive B cells determined. B cells, descended from the fetal liver inoculum (identified by their allotype) produced an antibody response to antigen in the presence of additional T cells, 15 days after transfer. Such a response could be prevented by injecting the recipient with alum-precipitated antigen (but not with deaggregated antigen) shortly after irradiation and reconstitution. This unresponsive state was specific and independent of afferent suppressor mechanisms. Mature B cells, on the other hand, were shown to be primed by alum precipitated antigen in irradiated reconstituted hosts. It was concluded that a fundamental difference exists between the responsiveness of mature and differentiating B lymphocytes. Tolerance in differentiating B lymphocytes is discussed in relation to the acquisition of self-tolerance.