As the main antibody-producing and antigen-presenting cells, B cells play critical roles in autoimmune diseases, tumors, and transplantation. Recently, the immunoregulatory functions of B cells have attracted attention and have been extensively studied in these fields. As a specific physiological status, pregnancy shares some common immunological characteristics with these diseases. Although many immune cells, such as natural killer cells, macrophages, and T cells, have been well studied during pregnancy, research focusing on B cells and their subsets during pregnancy has just begun.

According to their developmental trajectory, B cells can be divided into five major cell subtypes in the peripheral blood: transitional B cells (TrB cells), naive B cells, class-switched memory B cells (MBCs), nonclass-switched MBCs, and plasma cells, and these subtypes account for approximately 4%, 50%, 15%, 18%, and 5% of peripheral B cells in healthy individuals, respectively. 1 Although total B cells account for only 1-2% of decidual lymphocytes, we found that every stage of B-cell differentiation was present in the decidua in early pregnancy by flow cytometry (Fig. 1 a, b and Table S1). Naive B cells, class-switched MBCs, and nonclass-switched MBCs represented the predominant B-cell subsets, accounting for 26.5%, 33.3%, and 27.5% of the total B-cell population, respectively (Fig. 1 a and Fig. S1). In addition, total B cells and the TrB cell subset increased with increasing gestational weeks (Fig. 1 bg and Table S2). TrB cells and plasma cells comprised only a small portion of the total B-cell population (mean 2.04% and 0.73%, respectively)(Fig. 1 a). The existence of different proportions of the same B-cell subsets in the peripheral blood and local decidua supported the concept that B-cell differentiation occurs in local areas beyond the peripheral blood and secondary lymphoid organs. Similarly, there are specific lymphoid aggregates found in lung cancer known as tertiary lymphoid structures, in which B-cell-rich areas contain different B-cell subsets and T cell-rich zones. 2 TrB cells represent a unique subset of B cells at an intermediate stage between bone marrow immature B cells and peripheral mature B cells, and these cells are also known as human regulatory B cells (Bregs, with the immunoregulatory function of high IL-10 production). 3 Although there is a low percentage of TrB cells in peripheral blood, alterations in the frequency or function of TrB cells are associated with various autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and some