B cells develop from hematopoietic stem cells (HSCs) that originate from bone marrow. HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells. From here, their development into B cells occurs in several stages (shown in image to the right), each marked by various gene expression patterns and immunoglobulin H chain and L chain gene loci arrangements, the latter due to B cells undergoing V(D)J recombination as they develop.
Early B cell development: from stem cell to immature B cell
B cells undergo two types of selection while developing in the bone marrow to ensure proper development. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR. If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop. Negative selection occurs through the binding of self-antigen with the BCR; If the BCR can bind strongly to self-antigen, then the B cell undergoes one of four fates: clonal deletion, receptor editing, anergy, or ignorance (B cell ignores signal and continues development). This negative selection process leads to a state of central tolerance, in which the mature B cells don't bind with self antigens present in the bone marrow.
To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells. T2 B cells differentiate into either follicular (FO) B cells or marginal zone (MZ) B cells depending on signals received through the BCR and other receptors. Once differentiated, they are now considered mature B cells, or naive B cells.
While immature and during the T1 phase, B cells express BCR of class IgG, but BCR expression changes to the classes IgM and IgD after transition into the T2 phase and while mature up to activation.