C.Riedinger The lives of lymphocytes

B-cell T-cell

Generation Bone marrow Bone marrow

Maturation Bone marrow Thymus

Gene rearrangement of receptor

Bone marrow

Thymus

Selection Bone marrow -ve selection only

Thymus +ve (cortical epithelial cells) and –ve

Result Leave marrow as naïve (but mature) B-cells

Leave thymus as naïve (but mature) T-cells, either CD8+ or CD4+

Activation

Lymph nodes: • B-cell arrives from periphery

either naïve or having encountered AG, which it has internalised and displayed via MHCII (1st signal)

• B-cell meets T-cell = mutual activation: MHCII - TCR B7.1/2 - CD28 CD40 - CD40L

• In germinal centre: B-cell binds AG presented on follicular dendritic cell* • This contact with the AG allows

affinity maturation

Lymph nodes: (paracortex)

1. TCR engagement: TCR/CD4 - MHCII**

2. Engagement of co-stim molecules: CD28 - B7.1/2 (CD80/86) CD40L - CD40

Result Activated B-cell Activated CD4 TH0 cell Proliferation

and somatic hypermutation / affinity maturation

• Can now give help to CD8 cytotoxic T-cell

Class-switching

Downstream functions and differentiation Differentiation to plasma cell,

memory B-cell…

• Abundant AG • High affinity

AG binding • IL-12

TH1-cell

• Cell-mediated response

• IC pathogen • IFNγ, TNFβ

• Little AG • Weak affinity AG

binding • IL-4

TH2-cell

• Humoral response • EC pathogen • IL10

*Follicular dendritic cell: • NOT derived from bone marrow haematopoetic stem cells, but mesenchymal precursors • LACK MHC class II and express FEW pattern-recognising receptors • Do express complement receptors and FcγRIIb • They trap antigen opsonised by complement or antibodies and hold it at their surface in the

form of an AG/AB/C3d complex • Enable activated B-cells to form germinal centres

** any professional antigen-presenting cell