Primate B-1 Cells Generate Antigen-Specific B Cell Responses to T Cell–Independent Type 2 Antigens

Abstract

Antibody responses to T cell-independent type 2 (TI-2) antigens (Ag), such as bacterial capsular polysaccharides, are critical for host defense. In mice, B-1b cells expressing a CD11b+FSChiCD21lo/-CD19hi phenotype play a key role in producing antibodies against T cell-independent type 2 (TI-2) antigens (Ag). In primates, a distinct IgM+CD27+ “memory” B cell population is thought to generate TI-2 antibody responses and evidence for a B-1b-like cell population participating in these responses is lacking. Herein, we demonstrate that nonhuman primates (NHP; African green monkeys and cynomolgus macaques) harbor serosal B cells expressing a CD11b+FSChiCD21lo/-CD80+/-CD19hi phenotype, constitutively active Stat3, and increased reactivity with phosphorylcholine, similar to murine peritoneal B-1a and B-1b cell populations. Similar to what is observed for murine B-1b cells, NHP CD11b+FSChiCD21lo/-CD19hi B cells dominate the Ag-specific B cell response and antibody production against the TI-2 Ag, TNP-Ficoll. Although Ag-specific IgM+ B cells expressing CD27 were not detected prior to immunization, Ag-specific CD11b+CD19hi B cells expressed and maintained an IgM+IgDloCD27+CD80+ phenotype following immunization. Thus, the murine and NHP B cell populations responding to TNP-Ficoll are highly similar, with the main exception being that Ag-specific NHP B-1-like cells express CD27 following TI-2 Ag encounter. Therefore, murine B-1b and primate IgM+CD27+ “memory” B cell subsets proposed to produce TI-2 antibody responses may be highly related if not identical. Overall, these data not only support that B-1-like cells are present in NHP, but provide evidence that these cells perform the same functions attributed to murine B-1b cells.

PD-1 Suppresses Protective Immunity to Streptococcus pneumoniae through a B Cell–Intrinsic Mechanism

“…However, to date only T cell-intrinsic PD-1 signaling has been shown to regulate B cell responses (26, 34). PPS3 induced PD-1 expression on PPS3-specific B cells, some of which belonged to the B-1b cell subset, similar to that observed for hapten-specific B-1b cells from mice and non-human primates following immunization with NP- or TNP-Ficoll (35). Indeed, PD-1 may be a global suppressor of T cell independent responses, as PD-1 also suppresses Ab responses to haptenated Ficoll (16, 21), a T cell independent antigen that differs from PPS3 in several key respects (in contrast to PPS3 and many other types of PPS, it lacks co-associated bacterial contaminants that influence humoral responses (36), lacks charge, lacks tolerogenic potential, can be adjuvanted by TLR agonists (37), and localizes to different accessory cells (38, 39)).…”

Murine B-1 B Cell Progenitors Initiate B-Acute Lymphoblastic Leukemia with Features of High-Risk Disease

“…It is tempting to speculate based on the present data that B-1 progenitors were transformed in the patients with the highest lymphocyte counts. B-1 B cells have been described in non-human primates (32) and humans (33). It will be interesting, once human B-1 progenitors are resolved, to determine whether their response to oncogene expression differs from that of B-2 progenitors.…”

Developmental expression of B cell molecules in equine lymphoid tissues

“…B1 cells described in other species are enriched with BCRs that have specificity to PC (Lalor and Morahan, 1990, Griffin et al, 2011a and Yammani and Haas, 2013). A greater (p-value = 0.008) percentage of CD5 hi B cells (median 2.3%) in foal and adult horse PBL bound to the fluorescence-labeled PC than CD5 lo B cells (median 1.1%).…”

“…In addition, anti-PC antibodies produced by B1 cells have a role in protection against pneumococcal infection (Briles et al, 1982), reduction of atherosclerotic lesions (Shaw et al, 2000 and Kyaw et al, 2011), and clearing of apoptotic cells (Chen et al, 2009). Equine CD5 hi B cells are enriched for BCRs that can bind PC, as described in B1 cells of the mouse (Lalor and Morahan 1990), human (Griffin et al, 2011a), and non-human primates (Yammani and Haas, 2013). However, equivalent percentages of PC-specific human B cells have been shown to be CD5 hi and CD5 lo (Fiskesund et al, 2014).…”

“…B1 cells are enriched with BCRs that have specificity to phosphorylcholine (Lalor and Morahan, 1990, Griffin et al, 2011a and Yammani and Haas, 2013). Phosphorylcholine-specific B cells were identified by incubating 1×10 6 cells with 40μg/ml phosphorylcholine-BSA-fluorescein (PC-FITC, Biosearch Technologies, Petaluma, CA) at 37 °C in RPMI 1640 media with 5% FCS as previously described (Griffin et al, 2011a).…”