title: B cell repopulation after alemtuzumab induction-transient increase in transitional B cells and long-term dominance of naïve B cells.
abstract: In organ transplantation, the composition of the B-cell compartment is increasingly identified as an important determinant for graft outcome. Whereas naïve and transitional B cells have been associated with long-term allograft survival and operational tolerance, memory B cells have been linked to decreased allograft survival. Alemtuzumab induction therapy effectively depletes B cells, but is followed by rapid repopulation up to levels exceeding base line. The characteristics of the repopulating B cells are currently unknown. We studied the phenotypic and functional characteristics of B cells longitudinally in 19 kidney transplant recipients, before and at 6, 9 and 12 months after alemtuzumab induction therapy. A transient increase in transitional B cells and cells with phenotypic characteristics of regulatory B cells, as well as a long-term dominance in naïve B cells was found in alemtuzumab-treated kidney transplant recipients, which was not influenced by conversion from tacrolimus to sirolimus. At all time-points after treatment, B cells showed unaltered proliferative and IgM-producing capacity as compared to pretransplant samples, whereas the ability to produce IgG was inhibited long-term. In conclusion, induction therapy with alemtuzumab results in a long-term shift toward naïve B cells with altered phenotypic and functional characteristics.
authors.affiliation: Transplant Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Heidt
authors.forename: J
authors.initials: J
authors.lastname: Hester
authors.forename: S
authors.initials: S
authors.lastname: Shankar
authors.forename: P J
authors.initials: PJ
authors.lastname: Friend
authors.forename: K J
authors.initials: KJ
authors.lastname: Wood
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab