B cell activation and signal transduction

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Phosphorylation events in B cell activation:

Src kinases Lyn, Fyn, Blk
Syk

PLC
SLP/Btk
Grb2

SOS
RAS, MAPK

NAN (NFAT, AP-1, NFkB)

Complement receptor CD21 (CR2) activates BCR if the antigen is opsonized by C3b component of the complement.

CR2-CD19-CD81 complex is expressed on the surface of B lymphocytes.

Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses. Viruses, such as HIV and EBV, use the complement receptors (CR2) to the enter the cell. Genetic CD21 deficiency is associated with hypogammaglobulinemia (JACI, 2011).

When CD21 (CR2) interacts with C3d, the complex is brought into the BCR. CD19 has an ITAM that is phosphorylated, thus recruiting Lyn to enhance phosphorylation.

Bruton’s tyrosine kinase (Btk) is unique to B lymphocytes. Btk and Syk activate PLC

to break PIP2 down to IP3, and make DAG - this is analogous to the TCR pathway.

Btk is also involved in B lymphocyte maturation and loss of Btk causes Brutons’s

agammaglobulinemia, also called X-linked agammaglobulinemia.

B cell survival depends on survival and promoting signals such as BLYSS, BAFF, and APRIL. The receptors for these molecules include BR3, TACI and BCMA.

Activation of B cells depends on the following:

- CD 19 and CD21 (CR2)
- TAPA 1
- CD81
- ITAM (universal activation motif)

Inhibition of B cells depends on the following:

- CD22
- CD45
- FcγRIIb (CD32)
- CTLA-4 (Cytotoxic T-lymphocyte antigen-4)
- ITIM (universal inhibition motif)

CD22 is a B-lymphocyte cell adhesion molecule (BL-CAM)that binds sialic acid with an immunoglobulin (Ig) domain. CD22 is a member of Ig superfamily and SIGLEC family. CD22 is an inhibitory receptor for B cell receptor (BCR) signalling.

Fc gamma receptors for IgG (CD 16, 32, 64) are labeled in "reverse" order:

CD 16 - FcR III - low-affinity

CD 32 - FcR II - intermediate-affinity

CD 64 - FcR I - high-affinity

T and B Cells - Naive and Memory Cell Markers (click to enlarge the image).

Abatacept (Orencia) is CTLA4-human IgG1 fusion protein against B7-1 (CD80) and B7-2 (CD86). It is used for treatment of rheumatoid arthritis and juvenile rheumatoid arthritis.

T cell activation involves all of the following steps EXCEPT:

A. RAS-MAPK pathway

B. activation of Syk

C. activation of NFAT

D. activation of Protein Kinase C

Answer: B. Syk is part of the B cell activation. ZAP-70 is its equivalent in T cells.

References

Src (gene). Wikipedia.
LYN. Wikipedia.
Lck. Wikipedia.
SYK. Wikipedia.
LAT, Linker of activated T cells. Wikipedia.

Published: 08/29/2009
Updated: 10/29/2011