TY - JOUR
T1 - Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
AU - Pelissier, Aurelien
AU - Stratigopoulou, Maria
AU - Donner, Naomi
AU - Dimitriadis, Evangelos
AU - Bende, Richard J.
AU - Guikema, Jeroen E.
AU - Rodriguez Martinez, Maria
AU - van Noesel, Carel Jm
N1 - Funding Information: The authors thank Kostas Stamatopoulos laboratory for helping with the TRIP tool and for the fruitful discussions. We also thank Thera A M Wormhoudt for assisting in the experimental method development. We thank Nike Claessen for helping with the tissue preparation. This research was supported by the COSMIC European Training Network, funded from the European Union’s Horizon 2020 research and innovation program under grant agreement No 765158. Publisher Copyright: © 2023 Pelissier et al.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85168966504&partnerID=8YFLogxK
U2 - https://doi.org/10.26508/lsa.202301959
DO - https://doi.org/10.26508/lsa.202301959
M3 - Article
C2 - 37640448
SN - 2575-1077
VL - 6
JO - Life Science Alliance
JF - Life Science Alliance
IS - 11
M1 - e202301959
ER -