Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus

Abstract

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19⁺/CD27⁻ naive B cells more than CD19⁺/CD27⁺ memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27^high/CD38⁺/CD19^dim/surface Ig^low/CD20⁻/CD138⁺ plasma cells were found at high frequencies in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27^high plasma cells and naive CD27⁻ B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27⁺ B cells coexpressing IgD were memory B cells preferentially using V_H3 family members with multiple somatic mutations. CD27^high plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V_H4 family members. These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.