title: HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways.
abstract: OBJECTIVE
  Patients infected by the HIV type 1 (HIV-1) frequently show a general deregulation of immune system. A direct influence of HIV-1 particles on B-cell activation, proliferation and B-cell phenotype alterations has been recently described. Moreover, expression of activation-induced cytidinedeaminase (AID) mRNA, which is responsible for class switch recombination (CSR) and somatic hypermutation (SHM), was reported to be overexpressed in B cells exposed to HIV-1.
  
  
  METHODS
  Study of primary human B cells in an in-vitro model.
  
  
  METHODS
  In the current study, we evaluated which signalling pathways are activated in primary B cells after a direct contact with HIV-1 particles in vitro using different kinase inhibitors.
  
  
  RESULTS
  Here, we report that B-cell activation together with the increase of AID mRNA expression and the subsequent class switch recombination (CSR) in HIV-exposed B cells occurred through spleen tyrosine kinase (SYK) and c-Jun N-terminal kinase (JNK) pathways.
  
  
  CONCLUSIONS
  Therefore, we showed that HIV-1 could directly induce primary B-cell deregulation via SYK/B-cell receptor (BCR) engagement, and that activation was followed by the JNK pathway activation. To our knowledge, these data provide the first evidence that SYK/BCR activation was the first step for B-cell activation and CSR mechanism after HIV-1 stimulation in a T-cell-free context.
authors.affiliation: aLaboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria del Gregorio Marañón bNetworking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) cLaboratorio de Inmuno-regulación, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain.
authors.forename: Ana Judith
authors.initials: AJ
authors.lastname: Perisé-Barrios
authors.forename: Rafael
authors.initials: R
authors.lastname: Correa-Rocha
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernandez
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017578:Immunoglobulin Class Switching; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D048031:JNK Mitogen-Activated Protein Kinases