Anti-CD3ε induces splenic B220lo b-cell expansion following anti-CD20 treatment in a mouse model of allosensitization

Tsuyoshi Todo, Gordon Wu, Ning Ning Chai, Yao He, Gislaine Martins, Ankur Gupta, Jeffrey Fair, Nai You Liu, Stanley Jordan, Andrew Klein

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Antibodies targeting T cells and B cells are increasingly used for immunosuppression in clinical transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3ε alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3ε induced a discrete B220. lo, but not a conventional B220. hi subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220. lo cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220. lo cells were phenotypically similar to the B220. lo AA4.1. + CD23. - sIgM. lo sIgD. - developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220. lo cells, mice treated with combined anti-CD3ε/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3ε can induce an expansion of B220. lo B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response.

Original languageEnglish (US)
Pages (from-to)529-538
Number of pages10
JournalInternational immunology
Issue number8
StatePublished - Aug 2012
Externally publishedYes


  • Alloantibody response
  • B-cell homeostasis
  • B-cell phenotype
  • Flow cytometry
  • Skin allograft

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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