Molecular characterization of the cervical and systemic B-cell repertoire Unique, yet overlapping, immune compartments of an HIV-1 resistant individual

作者：Gaudet Ryan G; Breden Felix; Plummer Frank; Berry Jody D^*

来源：mAbs, 2011, 3(2): 181-191.

DOI：10.4161/epi.3.2.14858

• immunogenetics
• HIV-1
• B cells
• cervical mucosa
• somatic mutation
• HIV resistance

The cervical mucosa of women who are highly exposed to HIV-1, yet remain persistently seronegative (HEPS), presents a unique opportunity to study the dynamics of an immune compartment potentially capable of preventing HIV-1 infection. Herein, we provide a detailed characterization of the immunoglobulin repertoire of cervical and systemic B cells from one such HEPS individual from Nairobi, Kenya. Analysis was done on 512 V(H) sequences that were RT-PCR amplified from B cells in a paired sample from the cervix and peripheral blood. The V(H)3 and D(H) repertoire of class switched cervical B cells differs significantly from that of systemic B cells, indicating that the cervical environment affects local B-cell populations and hence V(H) gene expression. Six networks of clonally related, heavily mutated B cells were identified that spanned the systemic and cervical B-cell compartments. Analysis of somatic mutations suggests this is likely the result of systemic, class switched B cells homing to the cervical mucosa. Multiple networks of somatically mutated V-gene sequences, unique to the cervical mucosa, were also Identified This supports the notion that site specific responses occur and have unique regulation of tolerance and recruitment into local memory or blast B-cell compartments. We conclude that while the nature of the cervical environment shapes the local B cell repertoire, the infusion of post germinal center B cells to the human cervix is a common occurrence, and represents a means by which systemic immunization could provide the local antibodies necessary to prevent HIV-1 at the site of initial contact.

• 出版日期2011-4