A partial overview of the development and maturation of lymphocytes for undergraduate pathology in medical school.

1. C.Riedinger
The lives of lymphocytes
B-cell T-cell
Generation Bone marrow Bone marrow
Maturation Bone marrow Thymus
Gene
rearrangement Bone marrow Thymus
of receptor
Bone marrow Thymus
Selection
-ve selection only +ve (cortical epithelial cells) and –ve
Leave marrow as naïve (but mature) Leave thymus as naïve (but mature)
Result
B-cells T-cells, either CD8+ or CD4+
Lymph nodes:
• B-cell arrives from periphery
either naïve or having encountered Lymph nodes:
AG, which it has internalised and (paracortex)
displayed via MHCII (1st signal) 1. TCR engagement:
• B-cell meets T-cell = mutual TCR/CD4 - MHCII**
activation: 2. Engagement of co-stim molecules:
MHCII - TCR CD28 - B7.1/2 (CD80/86)
Activation B7.1/2 - CD28 CD40L - CD40
CD40 - CD40L
• In germinal centre:
B-cell binds AG presented on
follicular dendritic cell*
• This contact with the AG allows
affinity maturation
Result Activated B-cell Activated CD4 TH0 cell
Proliferation
• Can now give help to CD8 cytotoxic
and somatic hypermutation /
T-cell
affinity maturation
Class-switching • Abundant AG • Little AG
• High affinity • Weak affinity AG
AG binding binding
• IL-12 • IL-4
Downstream
functions and
differentiation
Differentiation to plasma cell, TH1-cell TH2-cell
memory B-cell…
• Cell-mediated • Humoral response
response • EC pathogen
• IC pathogen • IL10
• IFNγ, TNFβ
*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