title: Follicular T Cells from smB-Common Variable Immunodeficiency Patients Are Skewed Toward a Th1 Phenotype.
abstract: Germinal center follicular T helper (GCTfh) cells are essential players in the differentiation of B cells. Circulating follicular T helper (cTfh) cells share phenotypic and functional properties with GCTfh cells. Distinct subpopulations of cTfh with different helper capabilities toward B cells can be identified: cTfh1 (CXCR3+CCR6-), cTfh2 (CXCR3-CCR6-), and cTfh17 (CXCR3-CCR6+). Alterations in cTfh function and/or distribution have been associated with autoimmunity, infectious diseases, and more recently, with several monogenic immunodeficiencies. Common variable immunodeficiency (CVID) disease is the commonest symptomatic primary immunodeficiency with a genetic cause identified in only 2-10% of patients. Although a heterogeneous disease, most patients show a characteristic defective B cell differentiation into memory B cells or antibody-secreting cells. We investigated if alterations in CVID cTfh cells frequency or distribution into cTfh1, cTfh2, and cTfh17 subpopulations and regulatory follicular T (Tfr) cells could be related to defects in CVID B cells. We found increased percentages of cTfh exhibiting higher programmed death-1 expression and altered subpopulations distribution in smB-CVID patients. In contrast to smB+patients and controls, cTfh from smB-CVID patients show increased cTfh1 and decreased cTfh17 subpopulation percentages and increased CXCR3+CCR6+cTfh, a population analogous to the recently described pathogenic Th17.1. Moreover, Tfr cells are remarkably decreased only in smB-CVID patients. In conclusion, increased cTfh17.1 and cTfh1/cTfh17 ratio in CVID patients could influence B cell fate in smB-CVID patients, with a more compromised B cell compartment, and the decrease in Tfr cells may lead to high risk of autoimmune conditions in CVID patients.
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Cunill
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Clemente
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Nallibe
authors.initials: N
authors.lastname: Lanio
authors.affiliation: Immunology Department, Hospital Universitari Son Espases , Palma de Mallorca, Balearic Islands , Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Barceló
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Valero
authors.initials: V
authors.lastname: Andreu
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Pons
authors.affiliation: Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain; Human Immunopathology Research Laboratory, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Balearic Islands, Spain.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Ferrer
keywords: B cells; CVID; Th17.1 cells; follicular T helper cells; regulatory follicular T cells