Signaling Proteins and Transcription Factors in Normal and Malignant Early B Cell Development
(a) The Ig heavy and light chain genes are comprised of constant and variable regions, where the variable region is formed by an n number of segments termed V (variable), D (diversity), and J (joining) in the heavy chain and by segments V and J in the light chain. These segments are brought together by a site-specific recombination process termed VDJ recombination responsible for the extensive repertoire of BCR specificities. There are two loci for light chain, κ and λ. Here, all the loci are shown in germline configuration, previous to the process of VDJ recombination. (b) The early stages of B cell development are differentiated by the process of VDJ recombination, and the heavy (IgH) and light (IgL) chains are recombined in the proB and preB stages, respectively. Each stage is further subdivided according to the sequential assembly of the VDJ segments. Replication and recombination processes are mutually exclusive as denoted by the circular arrows and VDJ signs inside the cell. Dashed lines separating proB and preB stages indicate checkpoints where signaling from the preBCR and BCR is required for positive selection and progression along the B cell maturation pathway. Continuous lines indicate the main receptors controlling each developmental stage. The differential intensity in the IL-7 green line indicates the sub-stages where a higher or lower concentration of the IL-7R ligand is required.