PLC-γ2 is essential for formation and maintenance of memory B cells
Open accessAbstract
Resting antigen-experienced memory B cells are thought to be responsible for the more rapid and robust antibody responses after antigen reencounter, which are the hallmark of memory humoral responses. The molecular basis for the development and survival of memory B cells remains largely unknown. We report that phospholipase C (PLC) γ2 is required for efficient formation of germinal center (GC) and memory B cells. Moreover, memory B cell homeostasis is severely hampered by inducible loss of PLC-γ2. Accordingly, mice with a conditional deletion of PLC-γ2 in post-GC B cells had an almost complete abrogation of the secondary antibody response. Collectively, our data suggest that PLC-γ2 conveys a survival signal to GC and memory B cells and that this signal is required for a productive secondary immune response.
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BLNK is a central adaptor downstream of BCR, and PLCG2 is a major BCR proximal signaling node implicated in germinal center and memory B cell formation.
“Two further loci provide more direct mechanistic links to B cell receptor (BCR) signaling: BLNK is a central adaptor downstream of the BCR, and PLCG2 is a major BCR proximal signaling node implicated in germinal center and memory B cell formation.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [30]
The paper’s Abstract identifies PLC-γ2 as an important BCR-signaling component and reports that it is required for efficient germinal-center and memory B-cell formation. The Discussion mentions BLNK-deficient mice, but does not describe BLNK as a central adaptor downstream of the BCR. That part of the sentence is therefore unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral AD GWAS loci implicate B cell relevant genes including SCIMP, BLNK, PLCG2, HLA class II region and IGHG1.
“Indeed, several AD GWAS loci implicate B cell relevant genes as well, albeit with varying strength of evidence and confidence in causal gene assignment. These include SCIMP , BLNK , PLCG2 , HLA class II region and IGHG1 [26 -32].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [30]
IGHG1 is less well established as a causal AD gene and is more accurately described as residing within an AD associated locus rather than as a validated risk gene.
“IGHG1 , in contrast, is less well established as a causal AD gene and is more accurately described as residing within an AD associated locus rather than as a validated risk gene.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [30]
The Results discuss IgG1-positive B cells and PLC-γ2 in immunized mice, not IGHG1 as an Alzheimer’s disease risk gene. Searches for IGHG1, Alzheimer’s disease, and an AD-associated locus found no passage in our copy addressing the claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredHLA class II locus encompassing HLA-DRB1/HLA-DQA1 is a well established AD risk locus, although extensive linkage disequilibrium makes it difficult to pin down the specific causal gene.
“The HLA class II locus encom passing HLA-DRB1/HLA-DQA1 is also a well established AD risk locus, although extensive linkage disequilibrium across this region makes it difficult to pin down the specific causal gene.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [30]
The Discussion addresses PLC-γ2 signaling and memory B-cell maintenance, not Alzheimer’s disease risk. Searches for HLA-DRB1/HLA-DQA1, the HLA class II locus, and linkage disequilibrium found no passage addressing the claimed risk locus or difficulty identifying a causal gene. Page numbers were not available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredSCIMP is expressed across myeloid and B cell lineages and has been identified as an AD-associated locus.
“SCIMP is expressed accross myeloid and B cell lineages and has been identified as an AD-associated locus.”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [30]
The Results and Materials and Methods passages concern PLC-γ2 and memory B cells, not SCIMP. Searches for SCIMP expression across myeloid and B cell lineages and for an AD-associated locus found no passage addressing either claim in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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McHeyzer-Williams, M., Okitsu, S., Wang, N., & McHeyzer-Williams, L. (2012) · Nature Reviews Immunology · doi:10.1038/nri3128 · Cited by 449 · see citing works
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Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
- Authors
- Hikida, M., Casola, S., Takahashi, N., Kaji, T., Takemori, T., Rajewsky, K., & Kurosaki, T.
- Affiliations
- Kyoto University (JP)
- IFOM (IT)
- RIKEN (JP)
- Harvard University (US)
- Corresponding author
- Kurosaki, Tomohiro
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-03-09
- Volume
- 206
- Issue
- 3
- Pages
- 681-689
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2699133
- OpenAlex
- W2150827451
- Cited by
- 73
- References
- 5
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- PLCγ2, memory B cells, germinal center, B cell homeostasis, secondary antibody response, humoral immunity, survival signaling, conditional knockout mice, antigen-experienced B cells
- MeSH terms
- Animals, B-Lymphocytes, Cell Cycle, Cell Survival, Immunoglobulin G, Immunization, Immunologic Memory, Nitrophenols, Phenylacetates, Gene Deletion, Mice, Knockout, Germinal Center, Mice, Phospholipase C gamma
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