Natural occurrence and origin of somatically mutated memory B cells in mice.

Schittek, Birgit; Rajewsky, Klaus

doi:10.1084/jem.176.2.427

Cited by 64 publications

(58 citation statements)

References 51 publications

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“…Both subtypes are GC derived (35,36) and mediate host protection for a long period of time. In addition, there exist surface IgM + memory B cells exhibiting hypermutated BCRs that also persist over extended periods of time (11,12). Recently, it has been shown that these latter memory B cells constitute a proliferationcompetent pool of memory B cells that may differentiate into IgG + memory B cells upon antigenic challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Typically, memory B cells express isotype-switched IgG or IgA Igs on their surface. However, immunization with protein or polysaccharide Ags can also result in a pool of IgM + memory B cells (11)(12)(13)(14)(15). Memory B cells appear to efficiently recirculate throughout the lymphatic system and are found at comparable frequencies in all lymphoid organs as well as in the blood (16).…”

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confidence: 99%

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Viral Particles Drive Rapid Differentiation of Memory B Cells into Secondary Plasma Cells Producing Increased Levels of Antibodies

Zabel

Mohanan

Bessa

et al. 2014

The Journal of Immunology

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Extensive studies have been undertaken to describe naive B cells differentiating into memory B cells at a cellular and molecular level. However, relatively little is known about the fate of memory B cells upon Ag re-encounter. We have previously established a system based on virus-like particles (VLPs), which allows tracking of VLP-specific B cells by flow cytometry as well as histology. Using allotype markers, it is possible to adoptively transfer memory B cells into a naive mouse and track responses of naive and memory B cells in the same mouse under physiological conditions. We have observed that VLP-specific memory B cells quickly differentiated into plasma cells that drove the early onset of a strong humoral IgG response. However, neither IgM+ nor IgG+ memory B cells proliferated extensively or entered germinal centers. Remarkably, plasma cells derived from memory B cells preferentially homed to the bone marrow earlier and secreted increased levels of Abs when compared with primary plasma cells derived from naive B cells. Hence, memory B cells have the unique phenotype to differentiate into highly effective secondary plasma cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Viral Particles Drive Rapid Differentiation of Memory B Cells into Secondary Plasma Cells Producing Increased Levels of Antibodies

Zabel

Mohanan

Bessa

et al. 2014

The Journal of Immunology

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“…Nucleotides in codons 31 II , 38 III , 65 II , 100 II , 100 AII and III and 105 II (numbering according to Kabat & Wu 1991) have been described as mutational hot spots of the V H B1-8 gene (Fukita et al 1998;Schittek & Rajewsky 1992;Weiss & Rajewsky 1990). From a total of 52 breaks, two breaks occurred 5' of 38 III , ¢ve breaks 5' of 65 II and one break 5' of 100A III .…”

Section: Resultsmentioning

confidence: 99%

Indirect and direct evidence for DNA double–strand breaks in hypermutating immunoglobulin genes

Jacobs¹,

Rajewsky

Fukita

et al. 2001

Phil. Trans. R. Soc. Lond. B

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The generation of a diverse antigen receptor repertoire is fundamental for the functionality of the adaptive immune system. While the V(D)J recombination process that generates the primary antigen receptor repertoire is understood in great detail, it is still unclear by which mechanism immunoglobulin (Ig) genes are further diversi¢ed by somatic hypermutation. Using mouse strains that carry a non-functional, prede¢ned V H D H J H gene segment in their IgH locus we demonstrate DNA double-strand breaks (DSBs) in and around V H D H J H in B cells undergoing somatic hypermutation. The generation of these DSBs depends on transcriptional activity, and their distribution along the V H D H J H segment parallels that of point mutations in the hypermutation domain. Furthermore, similar to hot spots of somatic hypermutation, 50^60% of all DSBs occur preferentially at RGYW motifs. DSBs may transiently dissociate the Ig promoter from the intronic enhancer to block further transcription and to initiate an error-prone nonhomologous DSB repair pathway. In accord with this model large deletions are frequently produced, along with point mutations, in a V H D H J H segment inserted together with its promoter into the IgH locus in inverted orientation. Our data suggest that DSBs are reaction intermediates of the mechanism underlying somatic hypermutation.

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“…It has been shown in the murine system that slgD*" cells from adults show preferential expression of certain VH genes, indicating that they have already encountered environmental antigens and passed through a certain selection process in vivo [39,40]. It is also reported that sIgD'*' fraction from adult mouse contains antigen-specific memory B cells [41].…”

Section: Iga-and Iga2-producing Cells Induced In Neonatal and Adult Bmentioning

confidence: 99%

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals

Yachie

Konno

Ohta

et al. 1995

Clinical and Experimental Immunology

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SUMMARYNeonatal B cells with the naive (slgD"^) phenotype are able to generate IgG-and IgA-producing cells as well as IgM production in the presence of memory CD4'*' T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO'^) CD4"^ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgGl and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgGl and IgG3, although memory (sIgD") B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults' naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgAl, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgGl and IgG3 may be controlled by their own age-dependent maturation process.

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Natural occurrence and origin of somatically mutated memory B cells in mice.

Cited by 64 publications

References 51 publications

Viral Particles Drive Rapid Differentiation of Memory B Cells into Secondary Plasma Cells Producing Increased Levels of Antibodies

Viral Particles Drive Rapid Differentiation of Memory B Cells into Secondary Plasma Cells Producing Increased Levels of Antibodies

Indirect and direct evidence for DNA double–strand breaks in hypermutating immunoglobulin genes

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals

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