title: Importance of B cell co-stimulation in CD4(+) T cell differentiation: X-linked agammaglobulinaemia, a human model.
abstract: We were interested in the question of whether the congenital lack of B cells actually had any influence on the development of the T cell compartment in patients with agammaglobulinaemia. Sixteen patients with X-linked agammaglobulinaemia (XLA) due to mutations in Btk, nine patients affected by common variable immune deficiency (CVID) with <2% of peripheral B cells and 20 healthy volunteers were enrolled. The T cell phenotype was determined with FACSCalibur and CellQuest Pro software. Mann-Whitney two-tailed analysis was used for statistical analysis. The CD4 T cell memory compartment was reduced in patients with XLA of all ages. This T cell subset encompasses both CD4(+)CD45RO(+) and CD4(+)CD45RO(+)CXCR5(+) cells and both subsets were decreased significantly when compared to healthy controls: P = 0·001 and P < 0·0001, respectively. This observation was confirmed in patients with CVID who had <2% B cells, suggesting that not the lack of Bruton's tyrosine kinase but the lack of B cells is most probably the cause of the impaired CD4 T cell maturation. We postulate that this defect is a correlate of the observed paucity of germinal centres in XLA. Our results support the importance of the interplay between B and T cells in the germinal centre for the activation of CD4 T cells in humans.
authors.affiliation: Department of Immunology, Royal Free Hospital and University College London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Martini
authors.forename: V
authors.initials: V
authors.lastname: Enright
authors.forename: M
authors.initials: M
authors.lastname: Perro
authors.forename: S
authors.initials: S
authors.lastname: Workman
authors.forename: J
authors.initials: J
authors.lastname: Birmelin
authors.forename: E
authors.initials: E
authors.lastname: Giorda
authors.forename: I
authors.initials: I
authors.lastname: Quinti
authors.forename: V
authors.initials: V
authors.lastname: Lougaris
authors.forename: M
authors.initials: M
authors.lastname: Baronio
authors.forename: K
authors.initials: K
authors.lastname: Warnatz
authors.forename: B
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002469:Cell Separation; D002648:Child; D017074:Common Variable Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D054380:Receptors, CXCR5 / Q000096:biosynthesis
chemical_list: C095085:CXCR5 protein, human; D054380:Receptors, CXCR5; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D017493:Leukocyte Common Antigens