B Cell Development and Differentiation Markers

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.

B Cell Surface & Intracellular Markers at Different Stages of Development

Cell TypeHuman MarkersMouse Markers
Common Lymphoid ProgenitorCD10/Neprilysin+Lin-
CD34+CD117/c-kit-
Pax5+Sca-1/Ly6-
 Ly6D-
 IL-7 R alpha+
 Flt-3/Flk-2+
B Lymphocyte ProgenitorCD10/Neprilysin+Lin-
CD34+CD117/c-kit-
Pax5+Sca-1/Ly6-
 Ly6D+
 IL-7 R alpha+
 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 CellCD117/c-kitlowLin-
CD10/Neprilysin+B220/CD45 R+
CD34+CD19-
CD38+CD24low
Pax5+CD43+
 C1q R1/CD93+
 CD117/c-kit-
 CXCR4+
 Flt-3/Flk-2+
 IL-7 R alpha+
 IgM-
Pro-B CellCD117/c-kitlowLin-
CD10/Neprilysin+B220/CD45 R+
CD19+CD19+
CD20/MS4A1+CD24+
CD24+CD43+
CD34+CD117/c-kitlow
CD38+IL-7 R alpha+
C1q R1/CD93+IgM-
IL-3 R+ 
IL-7 R alpha+ 
Pax5+ 
Pre-B CellCD117/c-kit-Lin-
CD10/Neprilysin+B220/CD45 R+
CD19+CD19+
CD20/MS4A1+CD24+
CD24+CD43-
CD34-IL-7 R alpha+
CD38+IgM-
C1q R1/CD93+ 
IL-3 R+ 
IL-4 R alpha+ 
IL-7 R alpha+ 
Pax5+ 
Immature B CellCD117/c-kit-B220/CD45 R+
CD10/Neprilysin+CD19+
CD19+CD23/Fc epsilon RII-
CD20/MS4A1+CD24+
CD21+CD43-
CD24+C1q R1/CD93+
CD27-IgD-
CD38+IgM+
CD40+ 
C1q R1/CD93+ 
IL-4 R alpha+ 
IL-7 R alpha- 
B1a Cell CD1dmid
 CD5+
 CD19high
 CD23/Fc epsilon RII-
 CD43+
B1b Cell CD1dmid
 CD5-
 CD19high
 CD23/Fc epsilon RII-
 CD43+
Transitional B CellCD10/NeprilysinlowB220/CD45 R+
CD5+CD19+
CD19+CD21-/low
CD20/MS4A1+CD23/Fc epsilon RII-/low
CD21+CD24+
CD23/Fc epsilon RII+CD43-
CD24+C1q R1/CD93+
CD27-IgDlow
CD38+IgM+
C1q R1/CD93+B220/CD45 R+
TACI+CD19+
 CD21+
 CD23/Fc epsilon RII+
 CD24+
 CD43-
 C1q RI/CD93+
 IgD+
 IgM+
Marginal Zone B CellCD1c+B220/CD45 R+
CD19+CD1d+
CD20/MS4A1+CD19mid
CD21+CD21high
CD23/Fc epsilon RII-/lowCD23/Fc epsilon RII-
CD27+CD43-
FCRL3/FcRH3+C1q R1/CD93-
IgD-/lowIgDlow
IgM+/highIgMhigh
TACI+ 
Follicular B CellCD10/Neprilysin-B220/CD45 R+
CD19+CD1dmid
CD20/MS4A1+CD19mid
CD21+CD21low
CD22/Siglec-2+CD23/Fc epsilon RII+
CD23/Fc epsilon RII+CD43-
CD24lowCXCR5+
CD27-IgDhigh
CD38lowIgMlow
CXCR5+ 
IgD+/high 
IgM+/low 
TACI+ 
MHC class II+ 
Activated Germinal Center B CellCD19+B220/CD45 R+
CD20/MS4A1+CD19+
CD27+CD40+
CD38+MHC class II+
CD40+ 
CD83+ 
TACI+ 
MHC class II+ 
Memory B CellCD19+B220/CD45 R+
CD20/MS4A1+CD19+
CD21+CD21+
CD27mid/+CD27mid/+
C1q R1/CD93-CD40+
TACI+MHC class II+
PlasmablastBCMA+B220/CD45 Rlow
CD19lowCD19+
CD27highCD27high
CD38+CD38+
C1q R1/CD93+Syndecan-1/CD138+
Syndecan-1/CD138-/low 
Plasma CellBCMA+B220/CD45 Rlow
BLIMP1+BLIMP1+
CD19lowCD19-
CD20/MS4A1-/lowCD27high
CD27highCD38low
CD38highCXCR4high
Syndecan-1/CD138+Syndecan-1/CD138+
CXCR4+MHC class II-/low
MHC class II-/low 
Regulatory B CellCD1d+CD1d+
CD5+CD5+
CD19+CD19+
CD21+CD23/Fc epsilon RII-/low
CD24+CD24+
IL-10+C1q R1/CD93-/low
IL-35+TIM-1+
TGF-beta+IL-10+
 IL-35+
 TGF-beta+

Note: Lin- for Mouse CLP, BLP, B1, and B2 progenitor cells: CD3-, CD4-, CD8-, CD11b-, Gr-1/Ly-6G-, TER-119-

Lin- for Mouse Pre-Pro B, Pro-B, Pre-B cells: CD3-, CD11b-,  Gr-1/Ly-6G-, TER-119-