B-1a cells play an important role in mediating tissue homeostasis and protection against infections. They are the main producers of spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or to the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens.
Spleen_B-1a_TLRKO_2
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#2) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87686_pep.csv
PerC_B-1a_TLRKO_3
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#3) 7wk old Peritoneal Cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87688_pep.csv
PerC_B-1a_TLRKO_1
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#1) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87692_pep.csv
Spleen_B-1a_TLRKO_3
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#3) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87695_pep.csv
Spleen_B-1a_TLRKO_1
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#1) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87697_pep.csv
PerC_B-1a_TLRKO_2
Tlr2-/-Tlr4-/-Unc93b13d/3d C57BL/6 (Mus musculus) Female (#2) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87701_pep.csv
PerC_B-1a_TLR2x4dKO_2
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#2) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89642_pep.csv
Spleen_B-1a_TLR2x4dKO_1
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#1) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89641_pep.csv
Spleen_B-1a_TLR2x4dKO_3
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#3) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89640_pep.csv
PerC_B-1a_TLR2x4dKO_1
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#1) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89639_pep.csv
PerC_B-1a_TLR2x4dKO_3
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#3) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89638_pep.csv
Spleen_B-1a_TLR2x4dKO_2
Tlr2-/-Tlr4-/- C57BL/6 (Mus musculus) Female (#2) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
89637_pep.csv
PerC_B-1a_Unc3d_2
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#2) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87705_pep.csv
Spleen_B-1a_Unc3d_2
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#2) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87704_pep.csv
Spleen_B-1a_Unc3d_3
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#3) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87703_pep.csv
PerC_B-1a_Unc3d_3
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#3) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87702_pep.csv
Spleen_B-1a_Unc3d_1
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#1) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87700_pep.csv
PerC_B-1a_Unc3d_1
Unc93b(3d/3d) C57BL/6 (Mus musculus) Female (#1) 7wk old Peritoneal Cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87696_pep.csv
PerC_B-1a_WT_3
WT C57BL/6 (Mus musculus) Female (#3) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87698_pep.csv
PerC_B-1a_WT_1
WT C57BL/6 (Mus musculus) Female (#1) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87694_pep.csv
PerC_B-1a_WT_2
WT C57BL/6 (Mus musculus) Female (#2) 7wk old Peritoneal cavity B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87693_pep.csv
87691_pep
WT C57BL/6 (Mus musculus) Female (#2) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
Spleen_B-1a_WT_1
WT C57BL/6 (Mus musculus) Female (#1) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87689_pep.csv
Spleen_B-1a_WT_3
WT C57BL/6 (Mus musculus) Female (#3) 7wk old Spleen B-1a cells: IgH repertoire analysis by iRepertoire Inc.
87699_pep.csv