Abstract
We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.
Highlights
Immune responses to infectious agents have different out-comes that can either protect or fail to control disease
Antigenic challenge resulted in B cell activation and the development of significant numbers of CD19+HEL+AID/YFP+ B cells, which were not detected in non-immunized mice or in mice immunized in absence of helper T cells (Fig 1B)
The aim of this study was to characterize the fate of activated B cells and the generation of memory B cells
Summary
Immune responses to infectious agents have different out-comes that can either protect or fail to control disease. Protection from re-infection relies on the establishment of efficient secondary immune responses that require the generation of antigen-specific “memory” B and T lymphocytes. The generation and selection of T-cell dependent “memory” B cells involves distinct molecular mechanisms: immunoglobulin isotype recombination and somatic hyper mutation, both dependent on the expression of AID [1]. A long-standing paradigm defined memory B cells as IgM-IgG+ isotype switched cells [2]. It has been shown that some IgM+ B cells bear the phenotype of other memory cells, being CD27+, and carry frequent point mutations in the V region of the Ig genes, suggesting that they must represent highly selected B cell populations [3]. Populations of CD19+IgM+ able to mount secondary responses have been
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