Signaling Proteins and Transcription Factors in Normal and Malignant Early B Cell Development
B cell development in adult mammals starts in bone marrow with the commitment of hematopoietic stem cells (HSCs) to the B cell lineage and ends with formation of mature B cells in peripheral secondary lymphoid organs (e.g., the spleen). It is the sequential expression and assembly of the components of the B cell antigen receptor (BCR) what defines each developmental stage. The first stage exhibiting commitment to the B cell lineage is the proB, and here the immunoglobulin heavy chain is in the process of recombination, and the signaling proteins Igα and Igβ are in surface forming complexes with chaperon proteins like calnexin (the proBCR). The next developmental stage, the preB, happens after the heavy chain was successfully recombined and the preBCR is assembled. In this stage, the light chain is recombined and unrearranged heavy chain alleles are excluded. After light chain recombination and pairing with the heavy chain and Igα and Igβ the mature BCR is formed, the B cell is in the immature (in bone marrow) and transitional (in periphery) stages. Here, B cell mechanisms of self-tolerance are active allowing self- and nonself-recognition by the mature B cell. Transition to the mature stage happens if the BCR of the immature/transitional B cell does not find its cognate antigen after several days of bone marrow and peripheral trafficking.