Hematopoietic Stem Cell (HSC) Stage: B cell development begins with hematopoietic stem cells (HSCs), which are multipotent cells found in the bone marrow.
Lymphoid Progenitor Stage: HSCs differentiate into multipotent progenitor cells that can develop into either common myeloid or common lymphoid progenitor cells. Common lymphoid progenitor cells subsequently develop into B cells, T cells, or natural killer cells.
Pro-B Cell Stage: Lymphoid progenitor cells further differentiate into pro-B cells (progenitor-B cells) and start expressing certain markers and genes associated with B cell development. Pro-B cells multiply and develop within the bone marrow. Their development is supported by the release of interleukin-7 (IL-7) and other cytokines by bone marrow stromal cells.
Pre-B Cell Stage: Pro-B cells develop further to become pre-B cells (precursor-B cells). Pre-B cells are characterized by the expression of CD25, a component of the IL-2 receptor. IL-7 and other factors from the stromal cells help drive this maturation process, leading to the detachment of pre-B cells from stromal cells as adhesion molecules are reduced.
Immature B Cell Stage: Pre-B cells undergo a genetic rearrangement of the light chain and transition to the immature B cell stage. The immature B cells remain in the bone marrow, where they undergo positive and negative selection processes to ensure self-tolerance and eliminate those with receptors that react strongly to self-antigens.
Transitional B Cell Stage: The immature B cells that successfully pass the selection process leave the bone marrow and enter the bloodstream where they are known as transitional B cells. Transitional cells move through the bloodstream to secondary lymphoid organs such as the spleen and lymph nodes to continue their maturation.
Mature B Cell Stage: In secondary lymphoid organs, transitional B cells further differentiate into immunocompetent naïve mature B cells. The majority of the naïve mature B cells differentiate into follicular B cells, which further differentiate into long-lived plasma cells that produce antibodies or memory B cells. A small percentage of the naïve mature B cells become marginal zone B cells, which differentiate into short-lived plasma cells.
Mature B cells may be activated via two pathways - T cell-dependent activation or T cell-independent activation.