The induction of cytokine-producing B cells occurs following exposure to similar stimuli that are needed to induce antibody production, including activation of CD40, toll-like receptors (TLRs), and/or sequential linking of the BCR. However, research conducted over the last 40 years has revealed that B cell subsets at various stages of maturation also have the capacity to produce a wide array of cytokines. These cellular differentiation steps are well recognized for their involvement in effective humoral immune responses by leading to the production of high affinity antibodies to new and-through the generation of immunological memory-historical antigens. Innate-like B-1 cells have been shown to be formed during foetal and neonatal development and are a key player in the first-line defence against pathogens. Along with the BM-derived B cells, similarly to mice, humans are also thought to possess a subset of B cells known as B-1 cells. Upon recognition of antigen, mature naïve B cells can further differentiate into non-switched or switched memory B cells (CD19 +CD24 hiCD38 loCD27 +), short-lived plasmablasts (CD19 +CD24 loCD38 +CD27 +), and long-lived plasma cells (CD19 +/loCD38 +CD27 +CD138 +). In humans, immature B cells then exit the BM as transitional B cells (CD19 +CD24 hiCD38 hi) before they mature in the periphery as naïve B cells (CD9 +CD24 intCD38 int). The life cycle of a B cell starts in the bone marrow (BM), where haemopoietic stem cells rearrange the heavy chain and light chain loci to produce a functioning B cell receptor (BCR).
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