Development of B Cell Subpopulations in Humans and its Relevance to Malignancy

Abstract

B cell lineages are influenced by antigenindependent development and by immune activation when antigens stimulate the development of both memory B and plasma cell clones. It is difficult to investigate the origin of B cell malignancies without knowing the details of these physiological events. In 1974, Salmon and Seligmann [1] suggested that the various types of B lymphoid malignancies may derive from normal cells representing different levels of maturation. In addition, the degree of differentiation which takes place within the malignant clone also seems to be variable: some malignant cells, e. g. chronic lymphocytic leukaemia (CLL), are apparently “fixed” and unable to differentiate further, while in another disease, e. g. myeloma, the lymphoid or lymphoplasmacytoid “target cells” of malignancy differentiate into plasma cells. In our study we have, therefore, decided to approach the origin of B lymphoid disorders with a simple approach by asking the following questions: 1. What are the phenotypic features of B lymphocytes as they emerge in the normal bone marrow (BM) during childhood? The main aim here has been to find an answer to the question whether B cell populattions in the BM versus peripheral lymphoid organs have mutually distinctive features. 2. How do B cells develop in the normal fetus? Do B cells at different sites show distinct phenotypic features? In this part of study samples of fetal BM, para-aortic lymph nodes and spleen havee been studied. 3. Can B cell types (and the correspnding B cell malignancies) change their features when stimulated in vitro?