B Cell Development

B cell development in mammals takes place in the bone marrow. The process can be divided into two broad categories: 1) An antigen-independent development that produces B cells from hematopoietic stem cells, and 2) An antigen-dependent development that produces memory cells and further increases the specificity of the antibody. The stages in B cell development in bone marrow are marked by successive steps in rearrangement and expression of immunoglobulin (Ig) genes. The different B cell stages are the stem cell (also called the progenitor B cell), pro-B cell, pre-B cell, immature B cell, virgin B cell and plasma cell stages.B cells derive from pluripotent hematopoietic stem cells in the bone marrow. Stem cells differentiate into pro-B cells. The cell surface proteins that are expressed are CD43 and CD45. This cell is also unresponsive to IL-7 that is secreted from the stromal cells. These progenitor cells retain a limited capacity for self renewal, dividing to produce more pro-B cells as well as cells that will go on to develop further. CD43 and CD45 receptors are maintained from the stem cell stage, and as the cell develops further, CD19, HAS, RAG-1, RAG-2 and TDT are expressed. One of the most important events of the pro-B cell stage is the rearrangement of the Ig heavy chain genes. TDT functions here by randomly adding nucleotides to the junctions in Ig heavy chain genes. RAG proteins also function in the restructuring of the Ig heavy genes in conjunction with the DNA repair proteins expressed in the cell. The RAG proteins allow the repair enzymes to recognize the recombination site and subsequently cleave at that site. Ig-α, Ig-β, Mu and the surrogate light chains will form the pre-B cell receptor (pBCR) on the cell surface and facilitate further development through that signaling pathway. Memory B cells and Plasma B cells are quiescent and long-lived with the ability to survive in the absence of overt antigen for years.