Immunology: B cell development, pro and pre b cells

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B cells develop from hematopoietic stem cells (HSCs) that originate from bone marrow.[3] HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells.[3] 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.[4]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.[5][6] If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop.[5][6] 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).[6] 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.[4]

To complete development into mature b cells, immature B cells migrate from the bone marrow to the spleen as well as pass through two transitional stages: T1 and T2.[7] Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells.[8] Within the spleen, T1 B cells transition to T2 B cells.[8] 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.[9] Once differentiated, they are now considered mature B cells, or naive B cells.[8]

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