NDLI: Multimeric antibodies from antigen-specific human IgM+ memory B cells restrict Plasmodium parasites

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Multimeric antibodies from antigen-specific human IgM+ memory B cells restrict Plasmodium parasites

Content Provider	Scilit
Author	Thouvenel, Christopher D. Fontana, Mary F. Netland, Jason Krishnamurty, Akshay T. Takehara, Kennidy K. Chen, Yu Singh, Suruchi Miura, Kazutoyo Keitany, Gladys J. Lynch, Eric M. Miranda, Marcos C. King, Neil P. Kollman, Justin M. Crompton, Peter D. Long, Carole A. Pancera, Marie Rawlings, David J. Pepper, Marion
Copyright Year	2021
Description	Multimeric immunoglobulin-like molecules arose early in vertebrate evolution, yet the unique contributions of multimeric IgM antibodies to infection control are not well understood. This is partially due to the difficulty of distinguishing low-affinity IgM, secreted rapidly by plasmablasts, from high-affinity antibodies derived from later-arising memory cells. We developed a pipeline to express B cell receptors (BCRs) from Plasmodium falciparum–specific $IgM^{+}$ and $IgG^{+}$ human memory B cells (MBCs) as both IgM and IgG molecules. BCRs from both subsets were somatically hypermutated and exhibited comparable monomeric affinity. Crystallization of one $IgM^{+}$ MBC-derived antibody complexed with antigen defined a linear epitope within a conserved Plasmodium protein. In its physiological multimeric state, this antibody displayed exponentially higher antigen binding than a clonally identical IgG monomer, and more effectively inhibited P. falciparum invasion. Forced multimerization of this IgG significantly improved both antigen binding and parasite restriction, underscoring how avidity can alter antibody function. This work demonstrates the potential of high-avidity IgM in both therapeutics and vaccines.
Related Links	https://rupress.org/jem/article-pdf/218/4/e20200942/1411080/jem_20200942.pdf
DOI	10.1084/jem.20200942
Journal	The Journal of experimental medicine
Issue Number	4
Volume Number	218
Language	English
Publisher	Rockefeller University Press
Publisher Date	2021-03-04
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Antigen Antibody Igm Evolution Multimeric Sup Avidity Bcrs Mbcs Somatically Journal: The Journal of experimental medicine (Vol- 218, Issue- 4)
Content Type	Text

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