Teleost fish are the most primitive bony vertebrates that contain immunoglobulins, although belonging to different classes than those of mammals, having only IgM, IgD and IgT. No Ig maturation to more specific class is observed in fish, providing them with an antibody response that is slow and weak in terms of antigen affinity. This is the main reason why protection conferred by disease natural resistance or vaccination does not correlate with an antibody response. Despite these great differences, fish immunologists have always thought of fish B lymphocytes as the equivalent of mammalian conventional B2 lymphocytes, thus assuming many aspects of their functionality and leaving some possibilities unexplored.
However, many evidences strongly suggest that fish B lymphocytes do not act as mammalian B2 lymphocytes but closely resemble the B1 mammalian innate lymphocytes which are known to produce large amounts of IgM without previous exposure to the pathogen in a T-independent form.
Therefore, my main objective in this proposal is the phenotypical and functional characterization of fish B cells using the rainbow trout as a model. This will be performed with no restrictions derived from the assumption of roles ascribed in the basis of their homology to mammalian B2 lymphocytes, but in the light of the hypothesis that fish B lymphocytes resemble better a B1 model. This new context will enable me to explore possible functions and characteristics previously unexplored such as T cell independence, lack of antigen engagement, poly-reactivity of antibodies produced and role in pro-inflammatory responses.
The results obtained from this project may constitute a turning point on the field of fish immunology that should redefine previous unexplained results, having also practical repercussions for future vaccination strategies. Finally, fish B lymphocytes could become a model for humans B1 cells implicated in autoimmune diseases and leukaemias.
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