Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates.

Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GC) B cells. The human MBC compartment contains both switched IgG+ and unswitched IgM+ MBCs; however, whether these MBC subpopulations are equivalent in their response to B cell receptor cross-linking and their resulting fates is incompletely understood. Here, we show that IgG+ and IgM+ MBCs can be distinguished based on their response to κ-specific monoclonal antibodies of differing affinities. IgG+ MBCs responded only to high-affinity anti-κ and differentiated almost exclusively toward PC fates. In contrast, IgM+ MBCs were eliminated by apoptosis by high-affinity anti-κ but responded to low-affinity anti-κ by differentiating toward GC B cell fates. These results suggest that IgG+ and IgM+ MBCs may play distinct yet complementary roles in response to pathogen challenge ensuring the immediate production of high-affinity antibodies to homologous and closely related challenges and the generation of variant-specific MBCs through GC reactions.

Use of immunology in news and YouTube videos in the context of COVID-19: politicisation and information bubbles.

Background: The COVID-19 pandemic propelled immunology into global news and social media, resulting in the potential for misinterpreting and misusing complex scientific concepts. Objective: To study the extent to which immunology is discussed in news articles and YouTube videos in English and Italian, and if related scientific concepts are used to support specific political or ideological narratives in the context of COVID-19. Methods: In English and Italian we searched the period 11/09/2019 to 11/09/2022 on YouTube, using the software Mozdeh, for videos mentioning COVID-19 and one of nine immunological concepts: antibody-dependent enhancement, anergy, cytokine storm, herd immunity, hygiene hypothesis, immunity debt, original antigenic sin, oxidative stress and viral interference. We repeated this using MediaCloud for news articles.Four samples of 200 articles/videos were obtained from the randomised data gathered and analysed for mentions of concepts, stance on vaccines, masks, lockdown, social distancing, and political signifiers. Results: Vaccine-negative information was higher in videos than news (8-fold in English, 6-fold in Italian) and higher in Italian than English (4-fold in news, 3-fold in videos). We also observed the existence of information bubbles, where a negative stance towards one intervention was associated with a negative stance to other linked ideas. Some immunological concepts (immunity debt, viral interference, anergy and original antigenic sin) were associated with anti-vaccine or anti-NPI (non-pharmacological intervention) views. Videos in English mentioned politics more frequently than those in Italian and, in all media and languages, politics was more frequently mentioned in anti-guidelines and anti-vaccine media by a factor of 3 in video and of 3-5 in news. Conclusion: There is evidence that some immunological concepts are used to provide credibility to specific narratives and ideological views. The existence of information bubbles supports the concept of the "rabbit hole" effect, where interest in unconventional views/media leads to ever more extreme algorithmic recommendations.