B‐1 cells subsets challenged with Mycobacterium tuberculosis lipids differentiate into IgM antibody‐secreting cells
Ciara Ordoñez1,2, Musharaf Tarajia1,2, Hannah P. Savage5,6, René Rivera1, Cheyenne Weeks-Galindo1,6, Dilcia Sambrano1, Patricia L. Fernandez1, Nicole Baumgarth4,6, Amador Goodridge1 #
1 Tuberculosis Biomarker Research Unit, Center of Cellular and Molecular of Diseases (CBCME) at INDICASAT, 2 Acharya Nargajuna University, India, 4 Center for Comparative Medicine, University of California, Davis, CA, USA. 5 Department of Pathology, Microbiology and Immunology, UC Davis. 6 Sentara RMH Medical Center, Harrisonburg, VA, USA.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a reemerging disease with high mortality rates worldwide (Padayatchi, et al., 2019). The reinforcement of TB surveillance and early identification strategies has contributed to the progress in disease control and prevention (Duarte et al., 2019). But nevertheless; to adopt these strategies in high-incidence countries and reduce the global TB burden, we need alternative vaccines and potential biomarkers that complement the treatment with anti-TB drugs, follow up on patients with active pulmonary infection. In this investigation we proposed to evaluate the IgM antibodies secreted by B cells during the exposure of lymphocytes to different molecules. We tested the activation of mouse B cells by challenging them with common lipid molecules in bacterial pathogens. They were also incubated with Mycobacterium bovis BCG and with pure lipids extracted from Mycobacterium tuberculosis. With these ex-vivo bio-assays, we observed at cellular level that B cells respond to lipids and bacteria with the ability to secrete large amount of IgM antibodies and that by separating B cells by the expression of CD antigens on their surface we found that B-1 cell secretes IgM antibodies in response to lipids compared to B-2 subsets. Findings under in-vivo conditions also showed us that there is an IgM response in wildtype infected mice with Mycobacterium. These results that have already been published and other of our observations suggest that the B-1 cells that reside in the peritoneum are the ones that remain active and with the major responsibility to secrete IgM antibodies in response to the lipids from Mycobacterium tuberculosis; In our future research it would be interesting to explore if there an IgM contribution by active B-1 antibodies secreting cells at the site of the infection or as part of the circulating pool of immune cells of the lungs from infected mice with Mycobacterium.