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Sites of B Lymphocyte Selection, Activation, and Tolerance in Spleen

Journal of Experimental Medicine
The Rockefeller University Press
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The immune system appears to be rigid, restricting one lymphocyte to make one antibody (1) and the peripheral B cell pool to a constant number (108 in mice) (2– 4). To make a rapid immune response to an unlimited number of antigens at any anatomical site, it has developed at least three major strategies: (a) continuous production of 2 × 107 lymphocytes/d from bone marrow (mice; 5), displaying a part of the 1011 potential immunoglobulin repertoire (6); (b) the establishment of a long-lived B cell pool (108), under the influence of environmental antigens (7) or an idiotypic network (8, 9); and (c) the ability of long-lived B cells to migrate between different lymphoid tissues (10, 11), thus monitoring sites of antigen invasion. Since the 108 peripheral B cells have an average life span of months, <10% of the 2 × 107 B cells produced every day are expected to be recruited into the long-lived peripheral B cell pool (2–4). The question is: where and how does this selection take place? Splenic Outer Periarteriolar Lymphoid Sheath, the Site of Heavy Chain of the Valuable Region of Ig Gene (IgVH) Region–targeted Selection of Newly Produced B Cells into the Long-lived Peripheral B Cell Pool. Most newly produced B cells from bone marrow first migrate into the spleen through the terminal branches of central arterioles, arriving in the marginal zone blood sinusoids (Fig. 1 A). Both newly produced B cells and long-lived recirculating B cells can penetrate the marginal zone sinus, reaching the outer zone of the periarteriolar lymphocytic sheath (outer periarteriolar lymphoid sheath [PALS]). Although the long-lived recirculating B cells migrate further into the follicle, the majority of newly produced B cells appear to die within the outer PALS (2, 12). Thus, outer PALS may represent the site where a small proportion of the newly produced B cells are recruited into the long-lived pool. The selection signal has the following features: (a) it selects B cells according to heavy chain of t

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