Fig. 2

Lymphoid genesis and subset differentiation. a Differentiation of T cells (TC). Common lymphoid progenitors (CLP) migrate from bone marrow (BM) to thymus entering double-negative (DN, CD4-CD8-) stage (1). These cells initially express adhesion molecule CD44 and then α-chain of the interleukin (IL)-2 receptor (CD25), eventually lose CD44 and maintain CD25, rearrange T cell receptor (TCR) β chain, and then enter double-positive (DP, CD4+CD8+) stage (2), a transition stage of TC maturation. The DP TC then lose their membrane expression of CD25, rearrange their α chain, generate a complete αβ TCR, which has the capacity to recognize host major histocompatibility complex (MHC) molecules (positive selection), therefore survives and enters single positive (SP, CD4+, or CD8+) stage (3). After TC bind to MHCI, they become CD8+ TC and are termed as cytotoxic TC (Tc), whereas those binding to self-peptide–MHCII become CD4+ TC and are called as Naïve TC (T0). These SP TC then undergo “negative selection” to eliminate those that recognize MHC that bound to self-peptides, thereby completing the process of TC maturation. T0 cells can differentiate into effector TC (T helper cells Th1, Th2, Th17) and regulatory T cells (Treg) under the regulation of antigen (Ag) presentation, immune checkpoint, cytokine inducers, and metabolite-associated danger signal (MADS), and produce functional cytokines. b Differentiation of B cells (BC). In BM, B1/B2-specific CLP first differentiate into B1/B2 progenitor BC (pro-BC), B1/B2 precursor BC (pre-BC) with assembled pre-B cell receptor (BCR) and then became immature B1/B2 BC that express BCR and secrete IgM. Immature B1/B2 BC then migrate to spleen and differentiate into follicular (Fo) B2 BC, marginal zone (MZ) B2 BC, or mature B1 BCs, depending on the transcription factors that are induced by different signals. Fo BC can generate GC BC with follicular DC (a stromal cell) retained-Ag encounter and Tfh help. An affinity-matured Ab response then produce durable memory BC with high affinity to foreign Ag, as well as long lived plasma cells, which can secrete large quantities of Ab. B2 BC constitute the majority of splenic BCs. Mature B1 BC further differentiate into B1a secreting IgM and IL-10, and B1b producing IgM