B cell selection is a function of the post‐natal thymus

Abstract

Children with severe heart disease early in life may undergo cardiac transplantation in infancy. Attendant to that procedure, the thymus is removed in whole or part and mature T cells are depleted. These manipulations should cause the T cell repertoire to be severely contracted. Surprisingly, however, those who undergo cardiac transplantation in infancy are not immunodeficient suggesting that the T cell compartment adapts in early life to absence of the thymus and depletion of T cells. Whether the “adapted” T cell compartment provides optimal help for antibody production and development and/or maintenance of B cell memory is not known. To answer that question we studied mice subjected to removal of the thymus and/or T cell depletion. The number and phenotype of T cells in adult thymectomized mice was comparable to controls. Thymectomy did not perturb the development of B cells or T‐independent type 2 antibody responses. In contrast, thymectomy did profoundly impair B cell memory as depicted by decreased production of long‐lived antibody secreting cells in the bone marrow, and decreased antibody affinity maturation. Antibodies produced by thymectomized mice were encoded by heavy chain genes with CDR3 regions longer by 2 or 3 amino‐acids than the sham operated controls. Our findings indicate an unprecedented role for the adult thymus in B cell memory and in the selection of the peripheral B cell repertoire.