title: Unique B cell differentiation profile in tolerant kidney transplant patients.
abstract: Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance.
authors.affiliation: INSERM, UMR 1064, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Chesneau
authors.forename: A
authors.initials: A
authors.lastname: Pallier
authors.forename: F
authors.initials: F
authors.lastname: Braza
authors.forename: G
authors.initials: G
authors.lastname: Lacombe
authors.forename: S
authors.initials: S
authors.lastname: Le Gallou
authors.forename: D
authors.initials: D
authors.lastname: Baron
authors.forename: M
authors.initials: M
authors.lastname: Giral
authors.forename: R
authors.initials: R
authors.lastname: Danger
authors.forename: P
authors.initials: P
authors.lastname: Guerif
authors.forename: H
authors.initials: H
authors.lastname: Aubert-Wastiaux
authors.forename: A
authors.initials: A
authors.lastname: Néel
authors.forename: L
authors.initials: L
authors.lastname: Michel
authors.forename: D-A
authors.initials: DA
authors.lastname: Laplaud
authors.forename: N
authors.initials: N
authors.lastname: Degauque
authors.forename: J-P
authors.initials: JP
authors.lastname: Soulillou
authors.forename: K
authors.initials: K
authors.lastname: Tarte
authors.forename: S
authors.initials: S
authors.lastname: Brouard
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D016753:Interleukin-10
keywords: Apoptosis; B cells; cytokine; differentiation; tolerance; transplantation