分子病理学技术进展及临床应用

Apoptosis
No BCR
B Apoptosis
Centroblasts
Centrocytes
?
Post-Germinal Center
B cleaved cell
B non-cleaved cell
T lymphocyte
T lmmunocyte
Memory cell Plasma cell
Paradigm of Lymphocyte transform
by morphology and immunotyping considering molecular events
That is the beginning of our story today.
Understanding of Lymphocyte Development
1950s-2010
1. structure and function of lymphoid tissue
Germenal Center(GC)：structure，function，transformation
In the time, obviously Thomas Hodgkin did never know R-S cells in his cases before the microscope available in clinic.
While at present time, for us, what can be down with our naked eyes rather then with microscope or modern molecular techniques?
Understanding based on 70’s of last Century
Only by morphology
Lymphocyte transform in center of Follicle Interfollicle zone
FDC B lymphocyte
B lmmunocyte
Hilus
Medullary sinuses Efferent lymphatic vessels
Could you recognize the following cellular elements in lymph node?
T-zone
Germinal center Mantle zone Marginal zone
Understanding of B cell differentiation until 2005 by H Stein
Bone Marrow
T cell-rich zone
Germinal Center
Precursor B Lymphoblast
Somatic Hypermutation/ Affinity Maturation
Thymus-depending zone
Capsular and afferent lymphatics
Reticulum supporting lymphatic tissue
Cortex
Subcapsular sinus
Cortex
Follicle GC
Medulla
Trabeculae Medullary cords
B cell differentiation with anatomical sites of various stages
Could you recognize cellular elements as follows in lymph node?
T-zone
Germinal center Mantle zone Marginal zone
Lennert’s Presumption based on 80’s of last Century
Mantle zone
Germinal center Dark zone Light zone
Mantle zone Marginal zone
Centroblast Blast Immuoblast Macrophage FDC
Centrocyte T cell Macrophage FDC
Proliferation zone
Selected for apoptosis
On-going mutation
Update to B-lymphocyte development model in 2000’s
B cell differentiation by immuno-markers
V(D)J recombination
பைடு நூலகம்
Naive B cell
Intact BCR
Antigen
BCL2 ↓ BCL6 ↑
B B
B
B DC
BT
Increased Affinity
B
Decreased Affinity
Class Switching IGM → IgG, IgA
DC
T
B
B
BCL6 ↓ BCL2 ↑ IRF4 ↑ B
The cellular elements in lymphoid & hematopoietic tumors are the key to understand and diagnose their diseases.
Even more, the molecules in the related cells are the key, especially involved in the development and differentiation of lymphoid & hematopoietic cells
分子病理学技术进展及临床应用
(第一部分)
来自临床的问题
Contemporary Understanding of Carcinogenesis by molecular biology
as our introduction
More than 100 years ago (1830), British physician Thomas Hodgkin discovered a type of Lymphoma with his naked eyes.