Population Dynamics of Bone Marrow B Lymphocytes

The dynamic concepts of lymphocyte populations which heralded the era of modern cellular immunobiology have been generally substantiated by recent studies and are still being correlated with functional properties. B lineage cells in the bone marrow are dynamically heterogeneous: A large majority are newly-formed, rapidly renewed cells, continuously produced from precursor cells within the bone marrow and disseminated during a terminal maturation phase via the blood stream. These cells develop low densities of sIgM in the extravascular bone marrow parenchyma and may undergo some further maturation within bone marrow sinusoids. The rate of production of bone marrow B cells appears to depend partly on the total load of exogenous agents to which the individual is exposed. Bone marrow lymphocyte production maintains a population of rapidly renewed virgin B cells in the peripheral lymphoid tissues. A small proportion of these cells apparently may be selected to enter a long-lived pool of B cells if suitably activated. By continuously creating novel clonotypes this process potentially can anticipate new antigen challenges and allow the immune system to build up a repertoire of antigen specificities most appropriate to the individual's changing environment throughout life. A minority of B lymphocytes in the bone marrow comprises slowly renewed, long-lived cells which enter and leave the bone marrow parenchyma as a selective part of the recirculating lymphocyte pool in the blood stream. Their role in the bone marrow is unknown. They include antigen-specific B memory cells, yet these are not activated within the bone marrow itself. No regulatory role has yet been directly demonstrated. Recently activated B cells enter from the spleen after secondary antigenic stimulation to develop into antibody-producing cells within the bone marrow. In assessing the significance of any phenotypically or functionally distinct B cell subset in the bone marrow, a basic consideration is to assign the subset to one of the foregoing dynamic categories. Within a given category cells may represent one stage in a time sequence of development. The bone marrow also produces lymphocytes of as yet uncertain lineage and contains selected subsets of T cells. The roles of these cells in cytotoxic, regulatory, or other events remain to be elucidated.