CD21-/Low B Cells Are Increased in Both Common Variable Immune Deficiency (CVID) and Specific Antibody Deficiency (SAD)

Background: CVID and SAD are similar because of increased incidence of recurrent bacterial infections but CVID subjects have a higher risk for autoimmune complications. Increased percentages of CD21^-/low B cells reflect B cell activation and have been associated with autoimmunity. We sought to compare B cell sub-populations among patients with CVID with or without autoimmunity, SAD, and healthy individuals.

Methods: Using fresh whole blood samples multiple parameter flow cytometry analysis enumerated CD19/CD27 with extended markers including surface IgM/IgD and CD21 in 37 healthy controls (HC), 31 CVID subjects, and 8 SAD defined as subjects with recurrent infections and decreased antibody response to polysaccharide vaccine.

Results: There were no major differences in total CD19⁺ percentages among the groups. As expected CVID subjects had lower CD27⁺ memory B cells percentages compared to HC (14.2 ± 13.4% versus 33.0 ± 13.62% respectively, p < 0.05, Kruskal-Wallis method). Class switch recombination among CD27⁺ memory B cells was similar in SAD and HC (0.83 ± 0.39 versus 0.94 ± 0.62)).  Surprisingly, CD21^-/low B cells are increased in SAD, similar to CVID group (18.20 ± 26.35, 10.20 ± 12.59 respectively versus 6.70 ± 3.37 HC). 

Conclusions: Similar to CVID, subjects with SAD have increased CD21^-/low B cells but show percentages of class switched memory B cells similar to HC, indicating a distinct B cell phenotype. These findings suggest that B cells are activated in SAD but maturation and class switch recombination is not affected.