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HIV-1 induces B-cell activation and class switch recombination via spleen tyrosine kinase and c-Jun N-terminal kinase pathways

Perisé-Barrios, Ana Juditha,b; Correa-Rocha, Rafaela,c; Álvarez, Susanaa; Muñoz-Fernandez, Maria Ángelesa,b; Pion, Marjoriea,b

doi: 10.1097/QAD.0000000000000442
Basic Science

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.

Design: 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.

Conclusion: 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.

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.

Correspondence to Marjorie Pion, Laboratorio de Inmuno-Biología Molecular, Calle Dr Esquerdo 46, 28007 Madrid, Spain. Tel: +34 915868565; fax: +34 915868018; e-mail: marjorie.pion@salud.madrid.org

Received 26 February, 2014

Revised 5 August, 2014

Accepted 7 August, 2014

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© 2014 Lippincott Williams & Wilkins, Inc.