Journal
AGING CELL
Volume 21, Issue 10, Pages -Publisher
WILEY
DOI: 10.1111/acel.13705
Keywords
adaptive immunity; age-associated B cells; aging; influenza; TLR signals
Categories
Funding
- Foundation for the National Institutes of Health [NIDDK P30 DK034987, PO1AG01743, PO1AG021600, PO1AI46530, R01AI11882, R21AG058758, R21AG068313, R21AI1288, R25GM113686, R37AG025805, R37AI22125, T32 AI007349, T32 AI132152]
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This study found that the response to influenza A virus infection in aged mice is dominated by a specific population of B cells called infection-induced ABC (iABC). These iABC can produce neutralizing antibodies. Additionally, the study found that immunization with whole inactivated virus in aged mice also generates iABC. Therefore, IgD(+)ABC is likely to play a role as primary B cells that secrete antibodies and provide protection from infection in the aged.
Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas(+)GL7(-) effector B cell population we call infection-induced ABC (iABC). Most iABC express IgM and include antibody-secreting cells in the spleen, lung, and bone marrow. We find that in response to influenza, IgD(+)CD21(-)CD23(-)ABC are the precursors of iABC and become memory B cells. These IgD(+)ABC develop in germ-free mice, so are independent of foreign antigen recognition. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD(+)ABC can induce a faster recovery of weight and higher total anti-influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD(+)ABC are likely the naive B cells with the potential to become Ab-secreting cells and to provide protection from infection in the aged.
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