Abstract
IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. A majority of the IgM memory cells detected after day 30 post-infection, also T-bet-positive, had undergone somatic hypermutation, indicating they expressed activation-induced cytidine deaminase (AID). Therefore, to identify early AID-expressing precursor B cells, we infected an AID-regulated tamoxifen-inducible Cre-recombinase-EYFP reporter strain. Tamoxifen administration led to the labeling of both IgM memory cells and bone marrow ASCs on day 30 and later post-infection. High frequencies of labeled cells were identified on day 30 post-infection, following tamoxifen administration on day 10 post-infection, although IgM memory cells were marked when tamoxifen was administered as early as day 4 post-infection. Transcription of Aicda in the early plasmablasts was not detected in the absence of CD4 T cells, but occurred independently of TLR signaling. Unlike the IgM memory cells, the bone marrow IgM ASCs were elicited independent of T cell help. Moreover, Aicda was constitutively expressed in IgM memory cells, but not in bone marrow ASCs. These studies demonstrate that two distinct long-term IgM-positive B cell populations are generated early in response to infection, but are maintained via separate mechanisms.
Highlights
Memory B cells, in addition to long-lived plasma cells, provide a major component of immunological memory [1, 2]
activationinduced cytidine deaminase (AID) is expressed in GC cells, in our previous study we demonstrated that the IgM memory cells do not express markers characteristic of GC B cells [23]
Our findings reveal that both long-term antigen-specific IgM memory cells and bone marrow plasmablasts are derived from precursor cells present early during ehrlichial infection, well before the generation of canonical class-switched memory B cells that develop in GCs [45, 46]
Summary
Memory B cells, in addition to long-lived plasma cells, provide a major component of immunological memory [1, 2]. It has often been assumed that B cell memory is harbored in high-affinity class-switched immunoglobulin (swIg) B cells, it has become increasingly apparent that, as for T cells, the memory B cell compartment is diverse, and several different memory subsets exist [3,4,5]. IgM memory cells have been characterized in studies of murine memory responses following immunization, and similar cells are found in humans [12, 13]. IgM memory cells constitute a novel and important subset of long-lived memory B cells that may provide immunity to variant pathogens not recognized by classical high-affinity swIg memory B cells [14, 15]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.