Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

Matthias F Muellenbeck; Beatrix Ueberheide; Borko Amulic; Alexandra Epp; David Fenyo; Christian E Busse; Meral Esen; Michael Theisen; Benjamin Mordmüller; Hedda Wardemann

doi:10.1084/jem.20121970

Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

Matthias F Muellenbeck, Beatrix Ueberheide, Borko Amulic, Alexandra Epp, David Fenyo, Christian E Busse, Meral Esen, Michael Theisen, Benjamin Mordmüller, Hedda Wardemann

124 Citations (Scopus)

Abstract

Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.

Original language	English
Journal	Journal of Experimental Medicine
Volume	210
Issue number	2
Pages (from-to)	389-99
Number of pages	11
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20121970
Publication status	Published - 11 Feb 2013

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10.1084/jem.20121970

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title = "Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies",

abstract = "Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.",

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T1 - Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

AU - Muellenbeck, Matthias F

AU - Ueberheide, Beatrix

AU - Amulic, Borko

AU - Epp, Alexandra

AU - Fenyo, David

AU - Busse, Christian E

AU - Esen, Meral

AU - Theisen, Michael

AU - Mordmüller, Benjamin

AU - Wardemann, Hedda

PY - 2013/2/11

Y1 - 2013/2/11

N2 - Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.

AB - Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.

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DO - 10.1084/jem.20121970

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Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

Abstract

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