RESUMO
Upon Ag exposure, naive B cells expressing BCR able to bind Ag can undergo robust proliferation and differentiation that can result in the production of Ab-secreting and memory B cells. The factors determining whether an individual naive B cell will proliferate following Ag encounter remains unclear. In this study, we found that polyclonal naive murine B cell populations specific for a variety of foreign Ags express high levels of the orphan nuclear receptor Nur77, which is known to be upregulated downstream of BCR signaling as a result of cross-reactivity with self-antigens in vivo. Similarly, a fraction of naive human B cells specific for clinically-relevant Ags derived from respiratory syncytial virus and HIV-1 also exhibited an IgMLOW IgD+ phenotype, which is associated with self-antigen cross-reactivity. Functionally, naive B cells expressing moderate levels of Nur77 are most likely to proliferate in vivo following Ag injection. Together, our data indicate that BCR cross-reactivity with self-antigen is a common feature of populations of naive B cells specific for foreign Ags and a moderate level of cross-reactivity primes individual cells for optimal proliferative responses following Ag exposure.
Assuntos
Autoantígenos/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Reações Cruzadas/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Formação de Anticorpos , Diferenciação Celular , Células Cultivadas , Memória Imunológica , Ativação Linfocitária , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
At the outset of the COVID-19 pandemic, many medical students were removed from clinical duties and had their education put on hold. Some found novel ways to join efforts to respond to the pandemic. Georgetown University School of Medicine medical students created Medical Supply Drive (MSD or MedSupplyDrive), a 501(c)(3), on March 17, 2020, in response to the national shortage of personal protective equipment (PPE). This article reviews the formation of a national response to the pandemic, the methods employed to distribute PPE, and the results of MSD's work from March 17, 2020, through June 20, 2020. A focus was placed on equitable distribution, both within local regions and on the national scale, by distinguishing COVID-19 hotspots, including Native American reservations. As of June 20, 2020, over half a million items were donated, with 1,001 deliveries made to 423 hospitals, 182 clinics, 175 long-term care facilities, 25 homeless shelters, 32 public health departments, and 164 other facilities. From 46 states and the District of Columbia, 1,514 individuals volunteered, and 202 signed up as regional coordinators. MSD formed 2 international organizations, MedSupplyDrive UK and MedSupplyDrive Scotland, and established U.S.-based partnerships with 19 different PPE and aid organizations. MSD gained local, national, and international media attention with over 45 interviews conducted about the organization. While the pandemic temporarily disrupted formal medical education, MSD empowered medical students to actively learn about the needs of their communities and organize ways to address them while incorporating these values into their professional identities. The framework that this organization employed also provides a potential model for future disaster relief efforts in times of crisis. MSD hopes to motivate budding physicians to collaborate and play an active role in tackling public health inequities beyond hospitals and within the communities students will one day serve.