From the comments to the above, applicable to cancer.
IgG3 Vs IgG4 and the antitumor response.
I always like to cross check these things, to the immune system cancer cells are just another pathogenic invader to destroy.
As suspected this is important and the implications aren’t good.
B Cell Orchestration of Anti-tumor Immune Responses: A Matter of Cell Localization and Communication (2021)
somatic hypermutation (SHM)
“Additionally, analysis of more than 5,000 TCGA RNA-seq samples revealed that high levels of IgG3–1 switch are associated with prolonged survival in patients with high SHM rates, whereas IgG3–1 levels are not prognostic in low SHM samples, underscoring the role of SHM in generating BCR sequences with high binding affinity to the exposed tumor antigens (Hu et al., 2019).”
https://www.frontiersin.org/articles/10.3389/fcell.2021.678127/full
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How to select IgG subclasses in developing anti-tumor therapeutic antibodies (2020)
“IgG3 demonstrates the highest affinity binding to most FcγRs”
“IgG4 only has high affinity for FcγRI but weak affinities for all other receptors, and is a poor inducer of Fc-mediated effector functions.”
https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00876-4
lso found this – Fc-Fc interactions of IgG4 may affect immune evasion of cancers, regardless of the antigen specificity of the IgG4.
An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy
“We further found that IgG4, **regardless of its antigen specificity**, inhibited the classic immune reactions of antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity against cancer cells in vitro, and these effects were obtained through its Fc fragment reacting to the Fc fragments of cancer-specific IgG1 that has been bound to cancer antigens. We also found that IgG4 competed with IgG1 in reacting to Fc receptors of immune effector cells. Therefore, locally increased IgG4 in cancer microenvironment should inhibit antibody-mediated anticancer responses and help cancer to evade local immune attack and indirectly promote cancer growth. ”
https://pubmed.ncbi.nlm.nih.gov/32819973/