Investigation of CD۱۹+CD۲۱low B-cells expansion in primary immunodeficiencies

The expansion of a unique group of B-lymphocytes known as CD۱۹high CD۲۱low B-cells in peripheral blood has been suggested as a hallmark of autoimmunity in different entities. Their expansion also has been reported in diffuse large B-cell lymphoma (DLBCL). CD۲۱- DLBCL has been seen to predict poorer prognosis than CD۲۱+ DLBCL due to alteration in a cluster of genes implicated in immune response, cell cycle, antigen presentation, apoptosis, etc. Methods: We took blood samples from ۲۱ registered patients in the Iranian primary immunodeficiency registry (IPIDR) including patients with defects in LRBA, CTLA۴, Nf-KB۲, PI۳kR۱, RAG, and also ۱۸ healthy referents. Then, CD۱۹high CD۲۱low B-cells were separated by flow cytometry analysis. Data were analyzed using SPSS v.۲۷ software and applying correlation tests between variables. Results: Overall, the percentage of CD۱۹high CD۲۱low B-cells was slightly higher in patients with the defects. A distinctive investigation indicated that the rate was significantly higher in the PI۳kR۱ and LRBA groups. Interestingly, regardless of defect type, CD۱۹high CD۲۱low B-cell percentage in patients with reported autoimmunity was almost twice those without confirmed autoimmunity. Moreover, accumulation of CD۱۹ high CD۲۱low B-cells was strongly correlated with aging. Discussion: Our results confirm CD۱۹high CD۲۱low B-cells expansion as a marker of autoimmunity which increases by aging and probably more exposure to antigens. Since autoimmune disorders are serious complications of hematological malignancies, especially in DLBCL, CD۱۹high CD۲۱low B-cells assessment can provide an approach to determine prognosis and necessity of autoimmune management. Immunotherapeutic agents targeting the PD-۱/PD-L۱ signaling pathway can trigger or aggravate the condition through inhibition of its immunosuppression effect. On the other hand, PD-۱+ CD۴+ T-cells reduce the self-reactivity of CD۱۹high CD۲۱low B-cells and promote their receptor editing. Therefore, exclusive blockade of T regularity cells may attenuate inflammation and may provoke the immunosuppressive nature of Treg cells. Further studies may help depict the power of hypotheses and promise a potential approach to conducting immune regulation favorably via manipulating the PD-۱/PD-L۱ signaling pathway.

کلیدواژه ها:

CD۲۱low B-cells ، Immunodeficiency ، Autoimmune ، Lymphoma ، cancer