Resource competition as a mechanism for B cell homeostasis

Abstract

Cellular competition for survival signals offers a cogent and appealing mechanism for the maintenance of cellular homeostasis [Raff, M. C. (1992) Nature (London) 356, 397-400]. We present a theoretical and experimental investigation of the role of competition for resources in the regulation of peripheral B cell numbers. We use formal ecological competition theory, mathematical models of interspecific competition, and competitive repopulation experiments to show that B cells must compete to persist in the periphery and that antigen forms a part of the resources over which B cells compete.''The most basic qualities of a natural community are the kinds and numbers of species living in them.'' This quotation from a classic ecological monograph (1) could equally well apply to immunology, where the communities in question are populations of lymphocytes present within individual organisms. Motivated by this similarity in basic questions we have used ecological competition theory in studies of B cell homeostasis and diversity. A combination of laboratory and mathematical models lead us to propose that the size of the peripheral B lymphocyte pool results from a process of immigration from the bone marrow, competition for resources in the periphery (2), and rapid death of cells that fail to secure resources. Our models allow us to quantify the contribution of each of these three processes to the final size of the peripheral B cell pool.Immunologists often use the word competition and most would probably agree that they define competition as ''an interaction between two populations, in which, for each, the birth rates are depressed or the death rates increased by the presence of the other population'' (3). However, this type of interaction can arise through a number of different processes. In resource competition (1) the negative effects come about because the two populations both have a need for the same substrate that is in limited supply. In apparent competition (4) the two populations affect each others' growth via a shared predator rather than a shared resource. Other schemes have been proposed where populations affect each other directly or indirectly via populations on the same trophic level (5). It is useful to be precise about which type of process is envisaged when competition is invoked. Because such a formalism already exists in the ecological literature, it makes sense to adapt it to the special situation of cells competing within an organism. To go further and ask ''does the formalism fit the data?'' it becomes necessary to express the formal model in mathematical equations and see if those equations behave like the populations that we observe. This is the strategy we have adopted in the work presented here. We have developed formal schemes for competition among B lymphocytes that give rise to two models; one of competition in its broadest sense and one that is specifically a model of resource competition. We show detailed comparisons of our first model with our data on B lymphocyte population dynamic...

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