Convergent evolution and B-cell recirculation in germinal centers in a human lymph node

Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response wit...

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Vydáno v:Life science alliance Ročník 6; číslo 11; s. e202301959
Hlavní autoři: Pelissier, Aurelien, Stratigopoulou, Maria, Donner, Naomi, Dimitriadis, Evangelos, Bende, Richard J, Guikema, Jeroen E, Rodriguez Martinez, Maria, van Noesel, Carel JM
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Life Science Alliance 01.11.2023
Life Science Alliance LLC
Témata:
Animal models
Animals
Antigens
Autoimmune Diseases
B-Lymphocytes
Cloning
Competitive advantage
Germinal Center
Germinal centers
Humans
Immunization
Lymph Nodes
Lymphatic system
Lymphocytes B
Mice
Mutation
Phylogeny
Reproducibility
ISSN:2575-1077, 2575-1077
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Shrnutí:Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs.
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Aurelien Pelissier and Maria Stratigopoulou contributed equally to this work
Jeroen E Guikema, Rodriguez Martinez, and Carel JM van Noesel contributed equally to this work
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202301959