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 journalArticle

3 Citations (Scopus)

Abstract

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
Volume24
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Isoantibodies
B-Lymphocytes
B-Lymphoid Precursor Cells
T-Lymphocytes
Therapeutics
Allografts
Immunization
Homeostasis
Spleen
Skin
Isoantigens
Antibodies
Immunosuppression
Flow Cytometry
Transplantation
Bone Marrow

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Anti-CD3ε induces splenic B220lo b-cell expansion following anti-CD20 treatment in a mouse model of allosensitization. / Todo, Tsuyoshi; Wu, Gordon; Chai, Ning Ning; He, Yao; Martins, Gislaine; Gupta, Ankur; Fair, Jeffrey; Liu, Nai You; Jordan, Stanley; Klein, Andrew.

In: International Immunology, Vol. 24, No. 8, 08.2012, p. 529-538.

Research output: Contribution to journalArticle

Todo, T, Wu, G, Chai, NN, He, Y, Martins, G, Gupta, A, Fair, J, Liu, NY, Jordan, S & Klein, A 2012, 'Anti-CD3ε induces splenic B220lo b-cell expansion following anti-CD20 treatment in a mouse model of allosensitization', International Immunology, vol. 24, no. 8, pp. 529-538. https://doi.org/10.1093/intimm/dxs054
Todo, Tsuyoshi ; Wu, Gordon ; Chai, Ning Ning ; He, Yao ; Martins, Gislaine ; Gupta, Ankur ; Fair, Jeffrey ; Liu, Nai You ; Jordan, Stanley ; Klein, Andrew. / Anti-CD3ε induces splenic B220lo b-cell expansion following anti-CD20 treatment in a mouse model of allosensitization. In: International Immunology. 2012 ; Vol. 24, No. 8. pp. 529-538.
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AU - Liu, Nai You

AU - Jordan, Stanley

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