Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect

Alymphoplasia mice (aly/aly) have been shown to be deficient for a nuclear factor-kappaB-inducing kinase involved in signal transduction of lymphotoxi n beta receptor (LT-betaR) and of CD40, resulting in structural defects of secondary lymphoid organs and highly increased susceptibility to viral infe ctions. We analyzed the anti-viral immune response of bone marrow chimeras (BMC) between aly/aly mice and (C57BL/6 x DBA2)F1 mice(B6D2F1) to evaluate in vivo whether the structural defects of secondary lymphoid organs or intr insic B or T cell defects led to immunodeficiency in aly/aly mice. Transfer of aly/aly bone marrow into B6D2F1 mice (aly/aly-->B6D2F1) led to excellen t T but poor B cell reconstitution of recipients. Antiviral cytotoxic T cel l (CTL) responses of aly/aly-->B6D2F1 BMC were clearly improved compared to aly/aly mice whereas virus-neutralizing IgG reponses were virtually absent . Therefore, the inefficient CTL response was predominantly caused by the s tructural defect of secondary lymphoid organs and not by an intrinsic T cel l defect. In contrast, B cells of aly/aly origin were unable to undergo iso type switch after viral infections, indicating an intrinsic B cell defect i n vivo. Overall, aly/aly mice show the combined immunodeficient phenotype o f mice deficient for LT-betaR with B cells functionally deficient for CD40.