Dysfunction of CD27+IgD+ B cells correlates with aggravated systemic lupus erythematosus

Abstract

Objective: The apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). Natural IgM (nIgM) is important in clearing apoptotic cells and preventing them from triggering deleterious autoimmunity. B-1 and innate-like B (ILBs) cells are the main nIgM producers. Human CD27⁺IgD⁺ B cells (un-switched memory B cells) are considered ILBs. However, their functional properties in SLE remain undefined.

Methods: Peripheral blood sample of 50 SLE patients and 50 healthy controls were collected, and twelve SLE patients were assessed in a follow-up study. The amount of CD27⁺IgD⁺ B cell in each population was analyzed by flow cytometry. The IgM and IL-10 levels of CD27⁺IgD⁺ B cell were assessed by ELISPOT and qRT-PCR, respectively. SPSS 17.0 (SPSS, USA) was employed for data analysis. P < 0.05 indicated statistical significance.

Result: The amounts of CD27⁺IgD⁺ B cell were significantly decreased in SLE patients than healthy control (P < 0.01). CD27⁺IgD⁺ B cell amounts were positively correlated with WBC (r = 0.337, P = 0.017), platelet count (r = 0.396, P = 0.004), and serum C3 levels (r = 0.415, P = 0.003) and negatively correlated with serum creatinine levels (r = - 0.285, P = 0.045), SLEDAI(r = - 0.724, P = 0.000), and anti-dsDNA(r = - 0.477, P = 0.000). The IgM and IL-10 levels of CD27⁺IgD⁺ B in active SLE were decreased than healthy control (P < 0.001). Moreover, CD27⁺IgD⁺ B cells are increased in SLE cases after treatment than before treatment (P < 0.001).

Conclusion: The amounts of CD27⁺IgD⁺ B cell were significantly decreased in SLE patients compared with the healthy population, and CD27⁺IgD⁺ B cell was verified to be correlated with clinical and immunological features in SLE patients. CD27⁺IgD⁺ B cells had impaired function associated with IgM and IL-10 production in active SLE. Moreover, the amounts of CD27⁺IgD⁺ B cells were recovered to the normal level in SLE cases with treatment-related disease remission. Key Points • CD27⁺IgD⁺ B cell amounts are significantly decreased in SLE patients than healthy control. • CD27⁺IgD⁺ B cells are functionally impaired in producing natural antibody-like IgM and IL-10 in SLE patients. • CD27⁺IgD⁺ B cell amounts are correlated with clinical and immunological features in SLE.

Keywords: CD27+IgD+ B cells; Innate-like B cells; Natural IgM; Systemic lupus erythematosus.