Lymphocyte Production and Maturation

PRINCESS ALEN I. AGUILAR

Anatomical Origin

• Primary Lymphoid Tissue– BONE MARROW

(B cell)-Bursa– THYMUS (T cell)– CD34+ HSCs (NK cell)

• undergo antigen- independent lineage committment

• Most of the cells produced in the primary sites die before leaving; only a small percentage migrate to the secondary tissues.

• Secondary Lymphoid Tissue– Lymph nodes

– Spleen

– Tonsils

– Peyer patches in the intestine

– Weldeyer's Ring @ LN

• Proliferation of the T and B lymphocytes in the secondary or peripheral lymphoid tissues is primarily dependent on antigenic stimulation.

General Stages of Lymphocyte Maturation

THEY ARE CHARACTERIZED WITH THE USE OF ROMANOWSKY-STAINED FILMS: LIGHT MICROSCOPY

Hemocytoblast-immature cell in

the stem cell

Thymus

BoneMarrow

Lymphoid Stem cell

-give rise to 2 distinct progenitor cells

Progenitor T cell Progenitor B cell

Precursor B cell

Centroblast

Mature B cellsPeripheral blood

Plasma Cells

α/βPrecursor T cell

ϓ/8Precursor T cell

Mature T cell

BoneMarrow

Hemocytoblast-immature cell in

the stem cell

Thymus

Periphery

BoneMarrow

CFU-L-HLA-DR

-TdT

T cell

B cell Maturation

Progenitor B cell

•1st stage;No surface Ig•w/ CD19, CD40, CD45•rearrangement of gene•coding for the heavy chain @ Chromosome 14

Precursor B cell

•2nd Stage•w/ mu chain in the cytoplasm•rearrangement of gene coding for the light chain•Heavy chain appear w/o accompanying light chain because of CALLA detection

•2 light chains•kappa: Chrom2•Lambda:Chrom22

Immature B cell•IgM on the surface•Absence of CALLA•w/ CD21, CD35

•CD21-receptor for Epstein Bar Virus•IM-Infectious Mononucleosis

Mature B cell •Contains IgM and IgD

Activated B cell •Immunoglobulins G,M,A,D,E•PRODUCED BY PLASMA CELLS

B cell surface markers

Lymphocyte

• T-cell– LYMPHOKINES

• Tk or CTL• Th• Ts• DHTL-Respond

through production of chemotactic lymphokines

• others:– CSF– MIF– LyMIG– LCF– HCSF– T-cell activator factor– HLT

• B cell– Antibodies

• IgG-Goes to placenta• IgM-Mega• IgA-sAliva, teArs• IgD-Don't know fxn• IgE-allergEE

LYMPHOKINETICS

• Is the process of the lymphocyte maturation, multiplication, storage and migration to tissues, including sites of infeection or cell damage.

LYMPHOKINETICS

• Mitosis and Multiplication– Radioisotopic labeling

use for cell division, kinetics and life span of lymphocytes

– Pre B cells are rapidly dividing w/in 30-36 hrs to express B cells specific antigens

• in peripheral blood-this is the circulating lymphocyte that is lack T or B-cell surface markers

• Life Span• majority (78-89%) has

4 yrs life span but some can live as long as 10-20 yrs.

• about 11-22% of lymphocyte are short-lived, lasting 3-4 days

Lymphocyte Life Span and Circulation

• When unimpeded, they are generally moves in a characteristic manner- The nucleus is displaced forward by an elongated tail (uropod) of cyto plasm.– Uropod is the most adherent part of the cell

• Have to basic patterns of circulation:– (1) recirculation of the mature, differentiated lymphocyte

continually moving from one area of lymphatic system into another

– (2) Immature lymphocytes will travel from the BM to Thymus and from there to the peripheral and eventually to 20 lymphoid tissue that will migrate to thymus again via lymphatic vessels which is the long-lived T-lymphocytes.-THEY MAKE UP MOST OF THE RECIRCULATING POOL

– However it is thought that T lymphocytes has its own pathway-it is only some @ the Lymph nodes and gut areas

Accdg. to Turgeon

NORMAL REFERENCE VALUE• Approximately 5% of the total body lympho-

cyte mass is present in the circulating blood. • 60-80% of the blood lymphocyte pool in adults is

composed of T lymphocytes and approximately 20% is composed of B lymphocytes.

• Lymphocytes represent 31% of the total leukocytes present at birth; within a few days of birth, lymphocytes are the dominant type of leukocyte in the circulation. Most of the cells are T lymphocytes.

• In adults, lymphocytes represent approximately 34% of the total circulation of leukocytes, or 2.5 × 109/L.

Accdg. to Turgeon