B Cells,Viruses,and the SARS-CoV-2/COVID-19 Pandemic of 2020

This introduction to our “B Cells and Viruses in the Year 2020” issue in Viral Immunology was meant to be celebratory, but the celebration is quelled by a severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that is circling the globe (3,8). The virus, first identified in December 2019, is causing disease (COVID-19) that affects humans of all ages, particularly the elderly.

Currently (March 27, 2020), reports of virus infections are dramatically escalating. In total, there are >597,000 infections and 27,000 deaths among 177 countries or regions. Countries with the most reported infections are the United States (>104,000), Italy (>86,000), China (>81,000), and Spain (>65,0000) (4). In the United States alone, there are >1,700 deaths and 400 of these deaths were reported within the past 24-h period (9). Human B cells (and T cells) have not been sufficiently primed against the emergent SARS-CoV-2 to effectively prevent infection and disease. Experts in B cell (and T cell) research are called to action to provide knowledge and solutions. Immediate needs from B cell immunologists include diagnostic antibody reagents, virus-specific neutralizing polyclonal and monoclonal antibodies, and an effective vaccine (1).

How might immunologists harness lymphocytes as weapons against SARS-CoV-2 and other lethal viruses? Evolution has armed human lymphocytes with a sophisticated array of antibody and T cell receptors. During the development of each lymphocyte, gene rearrangements occur (involving V, D, and J gene fragments), resulting in the production of a unique cell surface receptor on each new cell (7). It has been predicted that V-D-J combinatorial diversity may supply humans with more than 10⁶⁰ different receptors (2), each with a different antigen target. The result is that humans have immune potential toward virtually any new pathogen in nature, including SARS-CoV-2. Since the 1700s, history has shown that virus look-a-like vaccines can be produced to prime virus-specific lymphocytes and activate protective immunity.

Once a human is exposed to antigens of a new respiratory virus like SARS-CoV-2, either by natural infection or with a look-a-like vaccine, antigen–antibody interactions at the appropriate B cell surfaces drive virus-specific cell proliferation, antibody isotype switching (through class switch recombination), cell maturation, and cell residence in systemic and mucosal sites. For respiratory viruses, cells and antibodies that reside in upper respiratory tract tissues are particularly effective in that they provide a first line of defense against virus at its point of entry (5,6). After priming against an acute respiratory virus, a healthy immune system is usually protective against future virus exposures and may provide convalescent antibodies for passive protection in naïve hosts (1). Immunity may be nonsterilizing (i.e., there may be limited virus replication after a second virus exposure), but lives are saved by rapid virus clearance and reduction of disease consequences. Even though humans may gain protective immunity from a natural SARS-CoV-2 exposure, the current consequences of COVID-19 at the population level are devastating. The scientific community is urged to develop passive antibody transfer programs and effective vaccines to provide immune protection before, not after, virus exposures.

The articles in this issue of Viral Immunology were written before the SARS-CoV-2 pandemic, but are timely in that they provide information necessary for the efficient recruitment and activation of B cells. Articles are categorized into two sections. Section 1 addresses how B cells work with articles from Lefkovits (A few key historical events in the antibody field: The alacritous antibody), New, King, and Kearney (Glycan reactive natural antibodies and viral immunity), Heltzel and Gearhart (What targets somatic hypermutation to the immunoglobulin loci?), Allie and Randall (Resident memory B cells), and Lam, Smith, and Baumgarth (B cell activation and response regulation during viral infections). Section 2 describes influences on B cell development, function, and survival with articles by Jones, Sealy, Penkert, Surman, Birshtein, Xu, Neale, Maul, Gearhart, and Hurwitz (From influenza virus infections to lupus: synchronous estrogen receptor α and RNA polymerase II binding within the immunoglobulin heavy chain locus), Johnson and Tarakanova (Gammaherpesviruses and B cells: Relationship that lasts a lifetime), Sala and Kuka (The suppressive attitude of inflammatory monocytes in antiviral antibody responses), Gyurova, Ali, and Waggoner (Natural killer cell regulation of B cell responses in the context of viral infection [see the cover of this issue to view the virus-induced congregation of natural killer cells [green], B cells [blue] and T cells [red] in the spleen]), and Penkert, Hankins, Young, and Hurwitz (Vaccine design informed by virus-induced immunity). Information in this issue of “B cells and viruses in the year 2020” may expedite the development of new diagnostics, prophylaxes, and therapies to prevent and treat COVID-19. If appropriately harnessed, the human immune system will serve as a formidable enemy against SARS-CoV-2 and any other viruses that threaten human lives.