Antigen presentation by B cells enables epitope spreading across an MHC barrier

Cecilia Fahlquist-Hagert; Thomas R. Wittenborn; Ewa Terczyńska-Dyla; Kristian Savstrup Kastberg; Emily Yang; Alysa Nicole Rallistan; Quinton Raymond Markett; Gudrun Winther; Sofie Fonager; Lasse F. Voss; Mathias K. Pedersen; Nina van Campen; Alexey Ferapontov; Lisbeth Jensen; Jinrong Huang; John D. Nieland; Cees E. van der Poel; Johan Palmfeldt; Michael C. Carroll; Paul J. Utz; Yonglun Luo; Lin Lin; Søren E. Degn

doi:10.1038/s41467-023-42541-7

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Ewa Terczyńska-Dyla, Kristian Savstrup Kastberg, Emily Yang, Alysa Nicole Rallistan, Quinton Raymond Markett, Gudrun Winther, Sofie Fonager, Lasse F. Voss, Mathias K. Pedersen, Nina van Campen, Alexey Ferapontov, Lisbeth Jensen, Jinrong Huang, John D. Nieland, Cees E. van der Poel, Johan Palmfeldt, Michael C. Carroll, Paul J. UtzYonglun Luo, Lin Lin, Søren E. Degn^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

12 Citationer (Scopus)

Abstract

Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

Originalsprog	Engelsk
Artikelnummer	6941
Tidsskrift	Nature Communications
Vol/bind	14
Nummer	1
Antal sider	21
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-023-42541-7
Status	Udgivet - dec. 2023

Adgang til dokumentet

10.1038/s41467-023-42541-7Licens: CC BY

Andre filer og links

Link to publication in Scopus

Citationsformater

Fahlquist-Hagert, C., Wittenborn, T. R., Terczyńska-Dyla, E., Kastberg, K. S., Yang, E., Rallistan, A. N., Markett, Q. R., Winther, G., Fonager, S., Voss, L. F., Pedersen, M. K., van Campen, N., Ferapontov, A., Jensen, L., Huang, J., Nieland, J. D., van der Poel, C. E., Palmfeldt, J., Carroll, M. C., ... Degn, S. E. (2023). Antigen presentation by B cells enables epitope spreading across an MHC barrier. Nature Communications, 14(1), Artikel 6941. https://doi.org/10.1038/s41467-023-42541-7

@article{96ec05d9989f48e7b5e22351fc70e24c,

title = "Antigen presentation by B cells enables epitope spreading across an MHC barrier",

abstract = "Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.",

author = "Cecilia Fahlquist-Hagert and Wittenborn, {Thomas R.} and Ewa Terczy{\'n}ska-Dyla and Kastberg, {Kristian Savstrup} and Emily Yang and Rallistan, {Alysa Nicole} and Markett, {Quinton Raymond} and Gudrun Winther and Sofie Fonager and Voss, {Lasse F.} and Pedersen, {Mathias K.} and {van Campen}, Nina and Alexey Ferapontov and Lisbeth Jensen and Jinrong Huang and Nieland, {John D.} and {van der Poel}, {Cees E.} and Johan Palmfeldt and Carroll, {Michael C.} and Utz, {Paul J.} and Yonglun Luo and Lin Lin and Degn, {S{\o}ren E.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-42541-7",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Fahlquist-Hagert, C, Wittenborn, TR, Terczyńska-Dyla, E, Kastberg, KS, Yang, E, Rallistan, AN, Markett, QR, Winther, G , Fonager, S, Voss, LF, Pedersen, MK, van Campen, N, Ferapontov, A, Jensen, L, Huang, J, Nieland, JD, van der Poel, CE, Palmfeldt, J, Carroll, MC, Utz, PJ, Luo, Y , Lin, L & Degn, SE 2023, 'Antigen presentation by B cells enables epitope spreading across an MHC barrier', Nature Communications, bind 14, nr. 1, 6941. https://doi.org/10.1038/s41467-023-42541-7

TY - JOUR

T1 - Antigen presentation by B cells enables epitope spreading across an MHC barrier

AU - Fahlquist-Hagert, Cecilia

AU - Wittenborn, Thomas R.

AU - Terczyńska-Dyla, Ewa

AU - Kastberg, Kristian Savstrup

AU - Yang, Emily

AU - Rallistan, Alysa Nicole

AU - Markett, Quinton Raymond

AU - Winther, Gudrun

AU - Fonager, Sofie

AU - Voss, Lasse F.

AU - Pedersen, Mathias K.

AU - van Campen, Nina

AU - Ferapontov, Alexey

AU - Jensen, Lisbeth

AU - Huang, Jinrong

AU - Nieland, John D.

AU - van der Poel, Cees E.

AU - Palmfeldt, Johan

AU - Carroll, Michael C.

AU - Utz, Paul J.

AU - Luo, Yonglun

AU - Lin, Lin

AU - Degn, Søren E.

PY - 2023/12

Y1 - 2023/12

N2 - Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

AB - Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

UR - http://www.scopus.com/inward/record.url?scp=85175556383&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-42541-7

DO - 10.1038/s41467-023-42541-7

M3 - Journal article

C2 - 37907556

AN - SCOPUS:85175556383

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6941

ER -

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater