A Splenic Marginal Zone-Like Peripheral Blood CD27 + B220 − B Cell Population Is Preferentially Depleted in HIV Type 1-Infected Individuals

Abstract

Peripheral blood CD27⁺ B cells are reduced in HIV-1-infected individuals. In healthy individuals, the human peripheral blood CD27⁺ B cell pool consists of two subsets defined by the expression, or lack thereof, of the CD45 isoform B220. We investigated the presence of circulating B220⁺ and B220⁻ memory B cells in HIV⁺ individuals and found that the reduction in CD27⁺ memory B cells occurs primarily among CD27⁺B220⁻ B cells. Studies conducted using healthy controls indicate that CD27⁺B220⁻ B cells have a splenic marginal zone like the immunophenotype IgM^hiIgD^loCD21⁺CD23⁻, express TLR9, and proliferate and secrete IgG and IgM in response to B cell-specific ODN. CD27⁺B220⁺ B cells have the immunophenotype IgM^loIgD^hiCD21⁺CD23⁺, express activation-induced cytidine deaminase, and proliferate in response to SAC but do not secrete immunoglobulin. The AICD expression, along with CD86 expression, by CD27⁺B220⁺ suggests these cells are of germinal center origin. The preferential depletion of CD27⁺B220⁻ B cells mirrors alterations in spleen morphology and resident B cell populations due to HIV infection reported by other investigators and may play an important role in the defective B cell immunity against T-independent pathogens such as pneumococcus observed in HIV-1-infected individuals.