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Author Notes:

Nicole Baumgarth: nbaumga3@jhmi.edu

Conceptualization: N. Baumgarth, F.L. Smith, H.P. Savage, and S. Keller. Methodology: F.L. Smith, N. Baumgarth, H.P. Savage, S. Keller, Z. Luo, C.M. Tipton, A.C. Apostol, A.E. Beaudin, D.A. Lopez, and I. Jensen. Investigation: F.L. Smith, H.P. Savage, Z. Luo, C.M. Tipton, I. Jensen, and S. Keller. Visualization: F.L. Smith, H.P. Savage, N. Baumgarth, A.C. Apostol, C.M. Tipton, and S. Keller, Funding acquisition: N. Baumgarth, A.E. Beaudin, and F.E.-H. Lee. Project administration: N. Baumgarth. Supervision: N. Baumgarth, A.E. Beaudin, and FEL. Writing—original draft: F.L. Smith and N. Baumgarth. Writing—review & editing: N. Baumgarth, F.L. Smith, H.P. Savage, C.M. Tipton, F.E.-H. Lee, A.E. Beaudin, I. Jensen, and S. Keller.

The authors would like to thank Tracey Rourke for expert help with flow cytometry, and Dr. Chengsong Zhu (University of Texas Southwestern, School of Medicine) for autoantibody analysis. We also thank Drs. Karen Hass (Wake Forest School of Medicine, Winston-Salem, NC, USA) for an anti-PCh IgM standard, Gregg Silverman (New York University, School of Medicine, New York, NY, USA) for anti-PCh and anti-PtC IgM standards, and Dr. Aaron Kantor (Stanford University School of Medicine, Stanford, CA, USA) for PtC liposomes.

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Research Funding:

This work was supported by National Institutes of Health/National Institutes of Allergy and Infectious Diseases grants R01AI117890, R01AI148652, and R21AI151995 (to N. Baumgarth), T32 OD011147 (to F.L. Smith), R01AI121252, P01AI125180, and U01AI141993 (to F.E.-H. Lee); National Institutes of Health/National Heart, Lung, and Blood Institute grants R01HL147081 and K01 HL130753, as well as the Pew Biomedical Scholars Award and Hellman Fellow Award (to A.E. Beaudin); and The Research Council of Norway grant 268085 UiT and a travel grant from The Arctic University of Norway (to I. Jensen).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • HEMATOPOIETIC STEM-CELLS
  • LY-1 B-CELLS
  • INFLUENZA-VIRUS
  • BONE-MARROW
  • AUTOANTIBODY PRODUCTION
  • POSITIVE SELECTION
  • ANTIBODY-RESPONSES
  • NEONATAL EXPOSURE
  • MICE
  • INNATE

B-1 plasma cells require non-cognate CD4 T cell help to generate a unique repertoire of natural IgM

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Journal Title:

JOURNAL OF EXPERIMENTAL MEDICINE

Volume:

Volume 220, Number 4

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Type of Work:

Article | Final Publisher PDF

Abstract:

Evolutionarily conserved, "natural" (n)IgM is broadly reactive to both self and foreign antigens. Its selective deficiency leads to increases in autoimmune diseases and infections. In mice, nIgM is secreted independent of microbial exposure to bone marrow (BM) and spleen B-1 cell-derived plasma cells (B-1PC), generating the majority of nIgM, or by B-1 cells that remain non-terminally differentiated (B-1sec). Thus, it has been assumed that the nIgM repertoire is broadly reflective of the repertoire of body cavity B-1 cells. Studies here reveal, however, that B-1PC generate a distinct, oligoclonal nIgM repertoire, characterized by short CDR3 variable immunoglobulin heavy chain regions, 7-8 amino acids in length, some public, many arising from convergent rearrangements, while specificities previously associated with nIgM were generated by a population of IgM-secreting B-1 (B-1sec). BM, but not spleen B-1PC, or B-1sec also required the presence of TCRαβ CD4 T cells for their development from fetal precursors. Together, the studies identify important previously unknown characteristics of the nIgM pool.

Copyright information:

© 2023 Smith et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/).
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