2- B lymphocytes

B cell maturation:

  • B cell maturation occurs in two phases
  1. in the bone marrow:

 Immature B cells are produced from the common lymphoid progenitors (CD34+) under influence of IL-17 that develop in the BM till IgM+ immature stage.

  1. in secondary lymphoid tissues:

When B cells reach the IgM+ immature stage, they migrate to secondary lymphoid tissues (such as the spleen, lymph nodes, Peyer's patches, etc.) where they are called transitional B cells; some of these cells differentiate into mature B lymphocytes. Somatic hypermutation, affinity maturation and memory B cell formation occurs in the germinal center of lymph nodes.

  • B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci.

Stage

Heavy chain

Light chain

Ig

IL-7 receptor

CD19

Progenitor (pro) B cells

germline

germline

-

Yes

No

Early Pro B cells

undergoes D-J rearrangement

germline

-

Yes

No

Late Pro B cells

undergoes V-DJ rearrangement

germline

-

Yes

Yes

Large precursor (Pre) B cells

is VDJ rearranged

germline

IgM heavy chain (Mu) in cytoplasm

Yes

Yes

Small Pre-B cells

is VDJ rearranged

undergoes V-J rearrangement

IgM heavy chain (Mu) in cytoplasm

Yes

Yes

Immature B cells

is VDJ rearranged

VJ rearranged

IgM on surface

No

Yes

Mature B cells

is VDJ rearranged

VJ rearranged

IgM and IgD on surface

No

Yes

Note that recombination of gene segments encoding Ig chain on one chromosome shuts off the other allele on the second chromosome (i.e. allelic exclusion) that ensure that each B cell express receptor of single antigen specificity.

  • B cell that expresses high affinity to self antigens encountered in the BM they will die by apoptosis (i.e. clonal deletion/negative selection) or reactivate recombinase enzyme to alter the specificity of their antigen receptors (i.e. receptor editing). This mechanism of central tolerance reduces the incidience of autoimmune diseases.
  • When the naïve mature B cell matches its specific antigen, the B cell proliferates and secretes a free form of those receptors (antibodies) with identical binding sites as the ones on the original cell surface.
  • After activation, the cell proliferates and B memory cells would form to recognize the same antigen.
  • CD20 is expressed on all stages of B cell development except the first and last; it is present from pre-B cells through memory cells, but not on either pro-B cells or plasma cells

B cell receptor:

(Diversity of B cell receptor: see chapter II)

  • B-cell receptor (BCR) is a transmembrane protein complex composed of membrane immunoglobulin (mIg) and disulfide-linked heterodimers called Iga/Igb. Molecules of this heterodimer associate with an mIg molecule to form a BCR complex.
  • mIg are usually membrane IgM and IgD, the antigen receptors of naive B cells, which have very short cytoplasmic tails. The cytoplasmic tail is too short to transduce signals.
  • The Iga/Igb molecules are required for signal transduction and surface expression of membrane Ig molecules.

 

 

TCR

BCR

Components

a and b chains

Heavy and light chains

domains

One V domain and one C domain in each chain

Heavy chain: one V domain and 3 or 4 C domains.

Light chain: one V domain and one C domain

Isotypes

3 a/b, g/d and NKT cells

2 (IgM and IgD)

Isotype switching

No

Yes

Number of combining sites to antigen molecule

1

2

Mobility

Rigid

Flexible (hinge region)

Antigen recognition

On APC associated with MHC

Direct

Nature of antigen that may be bound

Processed cell-bound peptide/MHC complex.

Unprocessed antigen, macromolecules (proteins, lipids, polysaccharides) and small chemicals.

Signal transduction molecules

CD3

Ig-a and Ig-b

Is secretion possible?

No (it is a cell surface molecule)

Yes (as antibodies in blood and body fluids)

 

 

B cell surface markers:

B cells express

  • BCR complex composed of membrane immunoglobulin (mIg) and disulfide-linked heterodimers called Iga/Igb.
  • CD19 which is used to enumerate B cells in the blood.
  • CD21 (complement receptor 2/CR2) allow the complement system to play a role in B-cell activation and maturation.
  • CD22 that functions as an inhibitory receptor for B cell receptor (BCR) signaling.
  • CD27 is a tumor necrosis factor receptor.
  • CD32 which is a receptor for Fc of IgG.
  • MHC-II.
  • CD40 needed for class switching.
  • Others as CD81, B7 and fas receptor.

 

 

Functions of B cells:

  1. Recognize antigen in soluble form by BCR.
  2. Mediate humoral immunity by antibody production.
  3. Act as APC.