Lymphopoiesis
Lymphopoiesis (lĭm'fō-poi-ē'sĭs) (or lymphocytopoiesis) is the generation of lymphocytes, one of the five types of white blood cells (WBCs).
Disruption in lymphopoiesis can lead to a number of lymphoproliferative disorders, such as lymphomas and lymphoid leukemias.
Lymphocytes are found in the bloodstream and originate in the bone marrow, however, they principally belong to the separate lymphatic system, which interacts with the blood circulation.
[citation needed] Lymphopoiesis is now usually used interchangeably with the term "lymphocytopoiesis" – the making of lymphocytes, but some sources distinguish between the two, stating that "lymphopoiesis" additionally refers to creating lymphatic tissue, while "lymphocytopoiesis" refers only to the creation of cells in that tissue.
[citation needed] The two classes of WBCs in mice originate from cells with strong stem cell properties – myeloids from the common myeloid progenitor (CMP), and lymphoids from the common lymphoid progenitor (CLP).
[1][page needed] It was eventually found these progenitors were not unique, and that the myeloid and lymphoid classes were not disjoint, but rather two partially interwoven family trees.
[1][page needed] In the case of mammals such as humans (Homo sapiens), lymphopoiesis begins with limited passive provision from the mother.
When such needs arise, new rounds of downstream lymphopoiesis, such as cell multiplication and differentiation, may occur, accompanied by intense mitotic and metabolic activity.
As the production of lymphocytes is so close to the central role of the immune response it is wise to approach the study of it with some humility in the face of the task.
Thus the following developmental states may be noticed in sequence in blood tests: Basic Map of T Cell lymphopoiesis This basic map of T Cell formation in sequence, is simplified and is akin to textbook descriptions, and may not reflect latest research.
Several stages at which specific regulators and growth factors are required for T cell development to proceed have been defined.
The most primitive cells in the thymus are the early thymocyte progenitors (ETP), which retain all lymphoid and myeloid potential but exist only transiently, rapidly differentiating into T and NK lineages.
See Gallery Image "Double Negatives" With the commitment to the T cell lineage, begins a very complex process known as TCR gene rearrangement.
Human NKT cells are a unique population and are thought to play an important role in tumor immunity[16] and immunoregulation.
[17] B lymphopoiesis occurs exclusively in the bone marrow and B lymphocytes are made continuously throughout life there in a 'microenvironment' composed of stromal cells, extracellular matrix, cytokines and growth factors, which are critical for proliferation, differentiation, and survival of early lymphocyte and B-lineage precursors.
The relative proportion of precursor B cells in the bone marrow remains rather constant throughout the life span of an organism.
A smaller subset (10–15%) called NK 'CD56 bright' is chiefly responsible for cytokine production and has enhanced survival.
Overall, a large number of DC of varying types are dispatched throughout the body, especially at epithelia such as skin, to monitor invaders and nibble their antigens.
(Medical Immunology, p. 122) Lymphocytes have a number of alarming properties such as the ability to wander around the body and take up lodging almost anywhere, and while on the way issue commands in the form of cytokines and chemokines and lymphokines, commands that affect many cell types in the body and which may also recursively induce further lymphopoiesis.
One strong behavior pattern that captivates researchers and the public alike is the ability of lymphocytes to act as police, judge and executioner to kill other cells or demand that they suicide, a command that is usually obeyed.
They select their targets based on typical molecules displayed by cells that are under stress by viral infection.
NKT cells are thought to play an important role in tumor immunity and immunoregulation (Medical Immunology, p. 135), yet little is known.
Because all WBCs are microscopic, colorless and often seemingly identical in appearance they are individually identified by their natural chemical markers, many of which have been analyzed and named.
HSCs are technically described as: lacking FMS-like tyrosine kinase 3 (Flt3) and lacking the markers specific to discrete lymphoid lineages (Lin) but expressing high levels of Sca1 and c-kit; HSC also express CD44, low levels of Thy1.1 (CD90), but no IL-7Ra or CD27.
However, beginning around 2000 and gaining momentum after 2005[25] in both studies in humans and mice, new complexities were noted and published in papers.
[citation needed] These studies are important now mainly to immunology researchers but are likely to eventually lead to changes in medical treatments.
In essence focus has been shifted away from the CLP to the MLP[citation needed] (lymphoid-specified progenitors), which are clearly lymphoid progenitors yet retain some myeloid potential, particularly the ability in both humans and mice to make macrophages – one of the most versatile of immune cell defenders – and also many dendritic cells, the best 'watchdogs' of antigen invaders.
However, whatever the details may turn out to be, the process of lymphopoiesis always seems to relentlessly give rise to progeny with special attributes and abilities – "superpowers" so to speak – but with progressively more restricted lymphoid developmental potential.
This model of lymphopoiesis had the virtue of relative simplicity, agreement with nomenclature and terminology, and is still essentially valid for the laboratory mouse.
pHSC, MPP and ELP cells are not fully committed to the lymphoid lineage because if one is removed to a different location it may differentiate into non-lymphoid progeny.
