AbuAttieh, Mouhammed

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.

Abstract Fitness of cell-mediated immunity is thought to depend on TCR diversity; however, this concept has not been tested formally. We tested the concept using JH−/− mice that lack B cells and have TCR Vβ diversity <1% that of wild-type mice and quasimonoclonal (QM) mice with oligoclonal B cells and TCR Vβ diversity 7% that of wild-type mice. Despite having a TCR repertoire contracted >99% and defective lymphoid organogenesis, JH−/− mice rejected H-Y-incompatible skin grafts as rapidly as wild-type mice. JH−/− mice exhibited T cell priming by peptide and delayed-type hypersensitivity, although these responses were less than normal owing either to TCR repertoire contraction or defective lymphoid organogenesis. QM mice with TCR diversity contracted >90%, and normal lymphoid organs rejected H-Y incompatible skin grafts as rapidly as wild type mice and exhibited normal T cell priming and normal delayed-type hypersensitivity reactions. QM mice also resisted Pneumocystis murina like wild-type mice. Thus, cell-mediated immunity can function normally despite contractions of TCR diversity >90% and possibly >99%.