B cell life span: A review

Abstract

Summary Debate has surroutided the subject of B cell life span since it was first measured in mice in the early 1970s. In the 25 years which have passed since then, it has become increasingly apparent that the methods employed to measure rates of B cell turnover, such as pH]-thymidine labelling, cell transfer or cell ablation, brought about significant disruptions to normal physiology which in themselves might have affected B cell turnover. More recently the use of bromodeoxyuridine has overcome many of these methodological difficulties and has allowed rates of B cell renewal to be measured within B cell subpopulations defined by multiparameter flow cytometry. Such studies have largely resolved the issue, concluding that about 85% of peripheral B cells are phenotypically mature and display first-order exponential kinetics defined by a half-life of 5-6 weeks, whilst the remainder are short-lived with a life span of several days. This review examines both traditional atid recent methods and discusses the influence of age, self-tolerance and randomness in the overall shaping of a kinetically stable mature B cell population.Key words: B cell. B cell life spanClonal selection depends on the presence of a diverse antigen-receptor repertoire. Control of the size, diversity and antigenic specificities of the B cell compartment is crucial to our understanding of how antibodies are produced. One critical variable which influences the composition of the B cell repertoire in vivo is the population life span of the cells within it. Despite this. B cell life span has evoked widespread controversy in the immunological community (see Immunology Today, Forum on B cell life spans. January 1993). It is known that B cells are produced continuously throughout the life of the host in sufficient numbers to replace the entire peripheral B cell pool within a matter of days.' If the life span of all B cells were as brief as this figure might imply, however, immunological memory could not reside at the cellular level and immune responses would necessarily depend on selection of B cells out of a repertoire derived exclusively from germ line Ig genes. On the other hand, if the majority of peripheral B cells were long-lived, immunological memory could reside at the cellular level, but its persistence would depend on cells with the greatest longevity. For this to occur, newly generated virgin B cells would need to undergo some fonn of selection before entering the long-lived compartment, a process which would play an essential role in shaping the composition of the B cell repertoire. Such a selection process might be random, based on antigen encounter, or might be influenced by anti-self .specificity. An appreciation of factors influencing B cell life span in the pre-immune and antigen experienced compartments can help us to conceptualize how the B cell repertoire develops and shed light on mechanisms of both B cell memory and tolerance.

Suboptimal Cross-linking of Antigen Receptor Induces Syk-dependent Activation of p70S6 Kinase through Protein Kinase C and Phosphoinositol 3-Kinase

“…(58,59). Thus, defining the mechanisms underlying B cell activation in response to varying degrees of receptor engagement is important in understanding B cell activation and tolerance.…”

Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice

“…Moreover, it was difficult to fully appreciate population dynamics in individual samples of human bone marrow. Proliferation and turnover of lymphocyte populations have been extensively studied in mice and rats following BrdU administration (32)(33)(34)(35). Therefore, human pre-B cells in chimeric marrow were discriminated by the presence of cytoplasmic H chains and absence of surface Ig L chains before simultaneous analysis of BrdU incorporation and presence of the Ki-67 Ag (Fig.…”

Suppression of allo-human leucocyte antigen (HLA) antibodies secreted by B memory cellsin vitro: intravenous immunoglobulin (IVIg) versusa monoclonal anti-HLA-E IgG that mimics HLA-I reactivities of IVIg

“…Classical B memory (B mem ) cells, such as those generated after infection, are antigen-experienced, disappearing from circulation in the absence of the immunizing agent and reappearing upon antigen re-exposure [1]. In contrast, the B mem /plasma cells that produce immunoglobulin (Ig)G antibodies against alloantigens secrete antibodies continuously without antigen exposure for > 20 years [2,3].…”