Importance of B cell co‐stimulation in CD4+ T cell differentiation: X‐linked agammaglobulinaemia, a human model

• Published in: Clinical and experimental immunology Vol. 164; no. 3; pp. 381 - 387
• Main Authors: Martini, H., Enright, V., Perro, M., Workman, S., Birmelin, J., Giorda, E., Quinti, I., Lougaris, V., Baronio, M., Warnatz, K., Grimbacher, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2011; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; Agammaglobulinemia - diagnosis; Agammaglobulinemia - genetics; Agammaglobulinemia - immunology; Analytical, structural and metabolic biochemistry; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; CD4+ T memory cells; CD4+CD45RO+CXCR5+ cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Differentiation; Cell Separation; Child; Common Variable Immunodeficiency - diagnosis; Common Variable Immunodeficiency - genetics; Common Variable Immunodeficiency - immunology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Genetic Diseases, X-Linked - diagnosis; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - immunology; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunologic Memory; Immunopathology; Leukocyte Common Antigens - biosynthesis; Lymphocyte Depletion; Male; Medical sciences; Middle Aged; Mutation - genetics; Protein-Tyrosine Kinases - genetics; Receptors, CXCR5 - biosynthesis; TFH cells; Translational Studies; XLA; Human; Immunopathology; TFH cells; CD4 T lymphocyte; Memory; CXCR5; Biochemistry; B-Lymphocyte; Cell differentiation; XLA; Genetic disease; CD4; cells; Immunoglobulinopathy; Infantile sex linked agammaglobulinemia; CD45RO; Costimulation; T memory cells; Models; Differentiation; Cell
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04377.x

Summary 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.