Precursor B Lymphocytes — Specific Monoclonal Antibodies and Genes

Abstract

The pool of mature, surface immunoglobulin (Ig) positive, antigen-sensitive B cells of a mouse has been estimated to contain 5 × 10⁸ to 10⁹ cells (Osmond 1986). Development from pluripotent stem cells and committed progenitors generates daily some 5 × 10⁷ cells, of which 3 × 10⁶ enter the pool of mature B cells. The same number of mature B cells must consequently die daily to keep the pool at a constant size. The immediate precursors of the mature B cells, called pre B cells, can be identified to be at various stages of their development by the genomic context in which their Ig gene loci are found. Thus, rearrangement of a D_H to a J_H segment on the Ig heavy (H) chain locus precedes that of V_H to D_HJ_H. This, in turn, is followed by rearrangements of the Igk light (L) chain and, finally, of the λ L chain locus (Tonegawa, 1983). No more than five divisions are estimated to occur from the earliest (i.e. at the time of D_H to J_H rearrangement) to the latest (i.e. at the time of surface Ig expression) state of their B lineage development in either fetal liver during embryogenesis or in bone marrow throughout adult life. The daily generation of 5 × 10⁷ cells must, therefore, be fed from more than 10⁶ B-lineage-committed progenitors and from stem cells. Very little is known of the forces that drive this early expansion of cells towards the B lineage, which should be antigen-independent, polyclonal and self-renewing, and might occur in fetal liver and bone marrow in contact with stromal cells.