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F Agenès

Publications and source records attributed to F Agenès.

3 recordsLinked to original sources

Peripheral B cell survival.

Recent findings suggest that lymphocyte survival is a continuous active process and support the role of B cell receptor engagement in B cell survival. In this context the conflict of survival interests between the diverse B cells gives rise to a pattern of interactions which mimics the behavior of complex ecological systems. In response to competition lymphocytes modify their survival requirements and diverge to occupy different immunological niches through differentiation. Thus naive and memory-activated B cell populations show independent homeostatic regulation. We discuss how niche differentiation allows the coexistence of different cell types and guarantees both repertoire diversity and efficient immune responses.

Animals↗

Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population.

We studied the role of bone marrow B cell production in the renewal of peripheral B cells and the feedback mechanisms that control the entry of newly formed B cells into the peripheral B cell pools. When resting lymph node B cells are injected into B cell-deficient hosts, a fraction of the transferred cells expands and constitutes a highly selected population that survives for prolonged periods of time by continuous cell renewal at the periphery. Although the number of donor B cells recovered is low, a significant fraction shows an activated phenotype, and the serum immunoglobulin (Ig)M levels are as in normal mice. This population of activated B cells is resistant to replacement by a new cohort of B cells and is able to feedback regulate both the entry of newly formed B cells into the peripheral pool and terminal differentiation. These findings suggest that peripheral B cell selection follows the first come, first served rule and that IgM-secreting cells are generated from a pool of stable activated B cells with an independent homeostasis.

Animals↗

Independent homeostatic regulation of B cell compartments.

In the present study we used mice with a developmental arrest of B cell production to study the ability of a limited number of normal B cell precursors to populate peripheral B cell pools. In chimeras reconstituted with mixtures of bone marrow (BM) cells from normal and B cell-deficient donors, we show that the rate of BM B cell production is a constant function of the number of BM pre-B cells and is not modified by the peripheral B cell pool size, i.e. there is no feedback regulation of the central pre-B cell compartment by the number of mature B cells. We also show that the physiological number of peripheral B cells requires a minimum continuous input of newly formed cells, but is not determined by the number of B cell precursors. Chimeras with a threefold reduced rate of BM B cell production have normal numbers of peripheral B cells. Parabiosis between normal and B cell-deficient mice showed that the BM B cell production of one mouse suffices to replenish the B cell pool of three mice. Finally, we show that the compartment of activated IgM-secreting B cells is homeostatically autonomous since the number of cells it comprises is regulated independently of the size of the mature B cell pool. The results presented here support a model of the immune system in which the size of the different B cell compartments, i.e. pre-B, resting B and IgM-secreting, is autonomously regulated.

Animals↗