Share this article on:

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:

Received 26 February, 2014

Revised 5 August, 2014

Accepted 7 August, 2014

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

© 2014 Lippincott Williams & Wilkins, Inc.