B-1 Cell
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B1 cells are a sub-class of
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s that are involved in the
humoral immune response Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it in ...
. They are not part of the
adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
, as they have no memory, but otherwise, B1 cells perform many of the same roles as other B cells: making
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s and acting as
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...
s. These B1 cells are commonly found in peripheral sites, but less commonly found in the blood. These cells are involved in antibody response during an infection or vaccination. There are two types of B1 cells subsets, B1a cells and B1b cells. B1b cells have been shown to be capable of memory responses. B1b cells also can recognize protective antigens in bacteria, which is unique because they are targeting something internal.


Origin

B1 cells are first produced in the
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
and most B1 cells undergo self-renewal in the periphery, unlike conventional B cells ( B2 cells) that are produced after birth and replaced in the
bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
.


Types

Human B1 cells have been found to have marker profile of CD20+CD27+CD43+CD70- and could either be CD5+ or CD5-, which has been debated since. CD5-CD72 is thought to mediate B cell-B cell interaction. What differentiates B1 cells from other B cells is the variable existence of CD5, CD86, IgM and IgD. B-1 B cells, in the mouse, can be further subdivided into B-1a (CD5+) and B-1b (CD5) subtypes. Unlike B-1a B cells, the B-1b subtype can be generated from precursors in the adult bone marrow. The B1a and B1b precursors have been reported to differ in the expression levels of CD138. Compared to B1a cells, B1b cells seem to recognize more types of antigens including intracellular antigens. Previously, B1b cell antigen recognition was thought to be random; however, recent research indicated that B1b cells specifically target a variety of protective antigens, also called conserved factors, over other types antigens. Recent functional studies indicate a further subdivision of labor assigning B1a cells as the producers of natural serum antibody (7). In contrast, B1b cells appear to be the primary source of dynamic T cell independent (TI) antibody production and long-term protection after bacterial infection such as ''
Borrelia hermsii ''Borrelia hermsii'' is a spirochete bacterium that has been implicated as a cause of tick-borne relapsing fever. It is spread by the soft-bodied tick ''Ornithodoros hermsi ''Ornithodoros hermsi'' is a species of soft tick. It can be infected ...
'' and ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...
''. These studies indicate preexisting subset differences in
B-cell receptor The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...
(BCR) specificity and antigen-driven B cell fate that remain important unresolved features of the system. B1a derived cells have a subset named innate response activator(IRA) B cells. IRA B cells produce
GM-CSF Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that ...
and IL-3. In
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
, they accumulate in
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
. This results in extramedullary
hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
and activating
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
.


Role in immune response

B1b cells are the most common B cells involved in antibody response during an infection or vaccination. This is because they can respond without receiving an activation signal from a T Helper cell. B1 cells express
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
in greater quantities than
IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
and its receptors show polyspecificity, meaning that they have low affinities for many different
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
. These polyspecific immunoglobulins often have a preference for other
immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, self antigens and common bacterial polysaccharides. B1 cells are present in low numbers in the
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
and
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
and are instead found predominantly in the
peritoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesothe ...
and pleural cavities. B1 cells generate diversity mainly via recombinatorial recombination (there is a preferential recombination between D-proximal VH gene segments). B1 cells characteristically express high levels of surface
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
(sIgM), demonstrable CD11b, and low levels of surface IgD (sIgD), CD21, CD23, and the B cell isoform of CD45R (B220). In adult mice, B1 cells constitute a minor fraction of the spleen and secondary lymphoid tissues but are enriched in the pleural and peritoneal cavities., B1 cells were shown to arise from precursors in the fetal liver and neonatal but not adult bone marrow and constitute the earliest wave of mature peripheral B cells. B1 cells express a separable BCR repertoire. Sequence analysis indicates antibodies with restricted sets of V region genes and an increased usage of λ light chains. B1 cells sequences also show no evidence for
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM dive ...
(SHM), and few non-templated nucleotide (N) sequence insertions, a pattern typical of neonatal B cells. Efficient B1 B cell development appears to be dependent on positive regulators of BCR signaling and the loss of negative regulators promotes greater accumulation of B1 B cells. Hence, there appears to be a role for self or foreign antigen in shaping the repertoire of the B-1 B cell compartment. B1 cells self-renew and spontaneously secrete IgM and IgG3 serum antibodies. These natural serum antibodies display extensive polyreactivity, demonstrable self-reactivity and bind to many common pathogen-associated carbohydrates. Natural serum antibodies play an important early role in the immune response to many bacteria and viruses but require complement fixation for effective antigen clearance. Innate sensing mechanisms can rapidly mobilize B1 cells regardless of specificity, highlighting the innate-like activity of this separate B cell compartment. B1b cells are known to be able to induce some type of memory, but their role in memory cells is unknown and may follow an untraditional route. B1b cells have effective and long-lasting responses to ''
Borrelia hermsii ''Borrelia hermsii'' is a spirochete bacterium that has been implicated as a cause of tick-borne relapsing fever. It is spread by the soft-bodied tick ''Ornithodoros hermsi ''Ornithodoros hermsi'' is a species of soft tick. It can be infected ...
'', ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...
'', ''
Salmonella Enterica ''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens. Epidemi ...
'', ''
Salmonella Typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of ''Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includin ...
'' and ''
Enterobacter cloacae ''Enterobacter cloacae'' is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium. Microbiology In microbiology labs, ''E. cloacae'' is frequently grown at 30 °C on nutrient agar or at 35 °C in tr ...
'' bacteria.


Laboratory isolation

In research laboratories, B1 B cells can be easily isolated from a mouse by injecting cell medium or
PBS The Public Broadcasting Service (PBS) is an American public broadcasting, public broadcaster and Non-commercial activity, non-commercial, Terrestrial television, free-to-air television network based in Arlington, Virginia. PBS is a publicly fu ...
into the peritoneal cavity of the mouse and then draining it off via a technique mirroring
diagnostic peritoneal lavage Diagnostic peritoneal lavage (DPL) or diagnostic peritoneal aspiration (DPA) is a surgical diagnostic procedure to determine if there is free floating fluid (most often blood) in the abdominal cavity. Indications This procedure is performed when ...
. Cells can be identified and placed into two categories "B1a" or B1b" using
flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...
looking for surface expression of
CD19 B-lymphocyte antigen CD19, also known as CD19 molecule ( Cluster of Differentiation 19), B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene ''CD19''. In humans, ...
,
B220 Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocy ...
, and CD5. B1a expresses high CD5 level, while B1b expresses low CD5 to almost-absent levels; both are CD19+ and B220low/-.


References

{{DEFAULTSORT:B-1 Cell B cells Lymphocytes Cells Human cells Immunology Immune system