Exploring the origins of adaptive immunity 2257946

Abstract Introduction Jawless vertebrates (Agnathans), such as the sea lamprey, persist today with minimal evolutionary changes compared to their first appearance on Earth nearly 500 million years ago. Unlike jawed vertebrates (Gnathostomes), lampreys evolved a distinct adaptive immune system that uses variable lymphocyte receptors (VLRs) instead of immunoglobulins as their antigen receptors. Their B- and T-like lymphocytes proliferate in response to antigenic stimulation, yet it remains unknown if these cell types coordinate together. Furthermore, lampreys lack canonical lymphoid organs such as spleen, bone marrow, and lymph nodes. Therefore, where do immune niches exist in the sea lamprey, and does coordinated lymphocyte response contribute to adaptive immunity? Methods We have transcriptionally characterized VLRA+ T-like cells and VLRB+ B-like cells in circulation. Furthermore, we have developed methods for flow cytometry and IHC in the blood, gills, liver, and intestine of the sea lamprey. We are assessing the sea lamprey for immune niches and the necessity of T-like cells in the adaptive immune response. Results We have transcriptionally characterized VLRA+ T-like cells and VLRB+ B-like cells in circulation. Furthermore, we have developed methods for flow cytometry and IHC in the blood, gills, liver, and intestine of the sea lamprey. Currently, we are assessing the sea lamprey for immune niches and the necessity of T-like cells in the adaptive immune response. Conclusion This work will provide insights into how a convergently evolved adaptive immune system functions and lay the foundation for future investigation into lymphocytes of the sea lamprey. Funding Source The Hypothesis Fund Topic Categories Veterinary and Comparative Immunology (VET)