Basic science for the clinician 38: B cells, factories, and immunomodulators

In a previous article in this series, we explored how developing pre-T cells learn how to be well-behaved T cells that recognize and honor the "self versus nonself" dichotomy of the universe. B cells do much of the same sort of thing, with multipotent stem cells becoming committed to ultimately becoming B cells within the bone marrow and then, after judicious culling of the flock, going off to the spleen to learn the final lessons needed to become "well-behaved" B cells. Like with T cells, there are a large number of things that can, and do, go wrong. If there is a failure of the system and B cells do not develop properly, hypogammaglobulinemia may develop as a result of a number of immune deficiency syndromes that can be quite devastating. If autoreactive cells survive to emerge into the periphery, autoimmunity, either organ-specific or more global, may occur. If B cells in the periphery proliferate in an uncontrolled fashion, a variety of B cell lymphoproliferative syndromes may develop, recognizable by the phenotypic markers of their originating B cell lineage level of differentiation. The full details of how autoreactive B cells survive and thrive, only to cause disease, are not yet clear, but identification of many of the phenotypic surface markers and circulating growth factors identified to this point have borne therapeutic fruit.