Final Report Summary - TEBLYM (Teleost B lymphocytes, the equivalent of mammalian B1 innate lymphocytes?) Fish are provided with an antibody response that is slow and weak in terms of antigen affinity, being this the main reason why natural or vaccine-conferred protection usually does not correlate with an antibody response in fish. Despite these great differences, fish immunologists have always thought of fish B lymphocytes in terms of the equivalent to mammalian conventional B lymphocytes (B2), the main subset of B lymphocytes that produces specific class-switched high-affinity antibodies against pathogens. However, our main hypothesis is that most fish B lymphocytes do not act as mammalian B2 cells but closely resemble mammalian B1 innate cells which are known to produce large amounts of IgM low-affinity antibodies without previous exposure to the pathogen and without help from T lymphocytes. These cells provide the host with a rapid poly-specific response that limits pathogen dissemination while highly-specific B2 responses are mounted. Therefore, the main objective of this project was the phenotypical and functional characterization of fish B cells with no restrictions derived from the assumption of roles ascribed in the basis of their homology to mammalian B2 lymphocytes, but in contrast to the light of the hypothesis that fish B lymphocytes resemble best a B1 model. Throughout the project, we have functionally and phenotypically characterized B cell subsets from different sources (blood, head kidney, spleen, intestine, gills), also focusing on tissues for which there was no previous information in teleost regarding B cell functionality (liver, different gut segments, adipose tissue). Many of these results confirm the hypothesis that fish B cells resemble both phenotypically and functionally mammalian B1 cells. For example, we have demonstrated that fish B cells express several B1-like markers such as CD5, CD6, CD11b and CD9. We have revealed that, in fish, B cells are one of the main cell types implicated in the early response to inflammation, directly responding non-specifically to antigens after their recognition by means of innate pattern recognition receptors. Other shared properties between mammalian B1 cells and fish B cells that we have demonstrated throughout the project include a long-term survival in cell culture, responsiveness to LPS and failure to proliferate in response to receptor cross-linking. Finally, in this project, we have identified a subpopulation of B cells in the gills that exclusively expresses IgD (and not IgM) on the cell membrane. This cell population identified for the first time in teleosts, is similar to the IgD+ B cell population found in the human upper respiratory tract. Our results have significantly advanced the state-of-the-art of fish B cell biology and have contributed to challenge the previously established paradigm that fish B cells resemble mammalian B2 cells.
