B cells are an integral part of the humoral immune response due to their ability to produce antibodies against foreign antigens. They originate from hematopoietic stem cells in the bone marrow, where they undergo several phases of antigen-independent development, leading to the generation of immature B cells. Immunoglobulin gene rearrangement during these early stages of B cell development results in the expression of a mature B cell receptor (BCR) that is capable of binding to antigen. This is followed by positive and negative selection processes, which are designed to eliminate non-functional and self-reactive immature B cells. Surviving B cells complete antigen-independent maturation in the spleen, producing immunocompetent naïve mature B cells, which subsequently develop into either follicular or marginal zone B cells. During the antigen-dependent phase of development, follicular B cells participate in germinal center reactions, where they differentiate into memory B cells or long-lived, antibody-secreting plasma cells. Defects in these developmental processes, selection, or B cell function have been linked with immunodeficiencies, autoimmune diseases, and cancer.

Cell Surface & Intracellular Markers Expressed at Different Stages of B Cell Development
Cell Type Human Markers Mouse Markers
Common Lymphoid Progenitor CD10/Neprilysin+ CD34+  Pax5+ Lin  CD117/c-kit  Sca-1/Ly6  Ly6D  IL-7 Rα+  Flt-3/Flk-2+
B Lymphocyte Progenitor CD10/Neprilysin+  CD34+  Pax5+ Lin  CD117/c-kit  Sca-1/Ly6  Ly6D+  IL-7 Rα+  Flt-3/Flk-2+
Mouse B1 Progenitor   Lin  B220/CD45 Rlow  CD19+  C1q R1/CD93+
Mouse B2 Progenitor   Lin  B220/CD45 R+  CD19  C1q R1/CD93
Pre-Pro B Cell CD117/c-kitlow  CD10/Neprilysin+  CD34+  CD38+  Pax5+ Lin  B220/CD45 R+  CD19  CD24low  CD43+  C1q R1/CD93+ CD117/c-kit  CXCR4+  Flt-3/Flk-2+  IL-7 Rα+  IgM
Pro-B Cell CD117/c-kitlow  CD10/Neprilysin+  CD19+  CD20/MS4A1+  CD24+  CD34+  CD38+ C1q R1/CD93+  IL-3 R+  IL-7 Rα+  Pax5+ Lin  B220/CD45 R+  CD19+  CD24+  CD43+  CD117/c-kitlow  IL-7 Rα+  IgM
Pre-B Cell CD117/c-kit  CD10/Neprilysin+  CD19+  CD20/MS4A1+  CD24+  CD34  CD38+ C1q R1/CD93+  IL-3 R+  IL-4 Rα+  IL-7 Rα+  Pax5+ Lin  B220/CD45 R+  CD19+  CD24+  CD43  IL-7 Rα+  IgM
Immature B Cell CD117/c-kit  CD10/Neprilysin+  CD19+  CD20/MS4A1+  CD21+  CD24+  CD27 CD38+  CD40+  C1q R1/CD93+  IL-4 Rα+  IL-7 Rα B220/CD45 R+  CD19+  CD23/Fcε RII   CD24+  CD43  C1q R1/CD93+ IgD  IgM+
B1a Cell   CD1dmid  CD5+  CD19high  CD23/Fcε RII   CD43+
B1b Cell   CD1dmid  CD5  CD19high  CD23/Fcε RII   CD43+
Transitional B Cell CD10/Neprilysinlow  CD5+  CD19+  CD20/MS4A1+  CD21+  CD23/Fcε RII +  CD24+ CD27  CD38+  C1q R1/CD93+  TACI+ T1: B220/CD45 R+  CD19+  CD24+  CD43  C1q R1/CD93+  IgM+  IgDlow
T2: B220/CD45 R+  CD19+  CD24+  CD43  C1q R1/CD93+  IgM+  IgD+
Marginal Zone B Cell CD1c+  CD19+  CD20/MS4A1+  CD21+  CD27+  FCRL3/FcRH3+  TACI+ B220/CD45 R+  CD1d+  CD19mid  CD21high  CD23/Fcε RII   CD43  C1q R1/
  IgMhigh  IgDlow
Follicular B Cell CD10/Neprilysin  CD19+  CD20/MS4A1+  CD21+  CD22/Siglec-2+  CD23/Fcε RII +  CD24low  CD27  CD38low  CXCR5+  TACI+  MHC class II+ B220/CD45 R+  CD1dmid  CD19mid  CD21low  CD23/Fcε RII +  CD43  CXCR5+
IgMlow  IgDhigh
Activated Germinal Center B Cell CD19+  CD20/MS4A1+  CD27+  CD38+  CD40+  CD83+  TACI+  MHC class II+ B220/CD45 R+  CD19+  CD40+  MHC class II+
Memory B Cell CD19+  CD20/MS4A1+  CD21+  CD27mid/+  C1q R1/CD93  TACI+ B220/CD45 R+  CD19+  CD21+  CD27mid/+  CD40+  MHC class II+
Plasmablast BCMA+  CD19low  CD27high  CD38+  C1q R1/CD93+  Syndecan-1/CD138/low B220/CD45 Rlow  CD19+  CD27high  CD38+  Syndecan-1/CD138+
Plasma Cell BCMA+  BLIMP1+  CD19low  CD20/MS4A1/low  CD27high  CD38high  Syndecan-1/ CD138+  CXCR4+  MHC class IIlow B220/CD45 Rlow  BLIMP1+  CD19  CD27high, CD38low  CXCR4high Syndecan-1/CD138+  MHC class II/low
Regulatory B Cell CD1d+  CD5+  CD19+  CD21+  CD24+  IL-10+  IL-35+  TGF-β+ CD1d+  CD5+  CD19+  CD23/Fcε RII /low  CD24+  C1q R1/CD93/low  TIM-1+ IL-10+  IL-35+  TGF-β+

Note: Lin– for Mouse CLP, BLP, B1 and B2 Progenitor cells: CD3– CD4– CD8– Gr-1/Ly-6G– Integrin aM/CD11b– TER-119– Lin– for Mouse Pre-Pro B, Pro-B, Pre-B cells: CD3– Gr-1/Ly- 6G– Integrin αM/CD11b– TER-119–