Accumulation of antigen-specific B and T cells in ectopic lymphoid tissue after immunization (99.11)

Abstract

Abstract Objective: Ectopic lymphoid tissue is associated with autoantibody production. Although reminiscent of authentic secondary lymphoid tissue, it is unclear if it can serve as a site of cognate T-B cell interactions leading to autoimmunity. This question was examined in mice with ectopic lymphoid tissue induced by tetramethylpecadentane (TMPD). Methods: B6 and BALB/c mice were treated i.p. with TMPD followed 3 mo later by s.c. immunization with NP-KLH or NP-OVA. NP specific B cells were identified by analysis of VH gene usage, flow cytometry, and ELISPOT. OVA transgenic T cells from DO.11 mice were transferred i.v. into BALB/c mice 3 d before immunizing with NP-OVA. OVA-specific T cells were identified by flow cytometry and proliferating B and T cells by BrDU staining. Results: 12 d after immunizing with NP-KLH, 90% of H chain genes from ectopic lymphoid tissue of B6 mice bore V186.2 or analogous NP-specific VH sequences. B cells stained by NP-PE were identified in ectopic lymphoid tissue by flow cytometry and secretion of anti-NP antibodies shown by ELISPOT. The ectopic lymphoid tissue and draining lymph nodes also had numerous OVA-specific T cells 7 d after immunization with NP-OVA and there was a progressive increase of BrDU+ T and B cells. Conclusion: The data suggest that following immunization, antigen-specific B and T cells undergo a local germinal center-like reaction within ectopic lymphoid tissue.