B-1 cell
Encyclopedia
B-1 cells are a sub-class of B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

 lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

s that are involved in the humoral immune response
Humoral immunity
The Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...

. They are not part of the adaptive immune system
Adaptive immune system
The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. Thought to have arisen in the first jawed vertebrates, the adaptive or "specific" immune system is activated by the “non-specific” and evolutionarily older innate...

,as they have no memory, but otherwise, B-1 cells perform many of the same roles as other B cells: making antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 against antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s and acting as antigen presenting cells (APCs). Notably, most B-1 cells do not develop into memory B cell
Memory B cell
Memory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...

s.

Origin

B-1 cells are first produced in the fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

 and most B-1 cells undergo self renewal in the periphery, unlike conventional B cells (B-2 cells) that are produced after birth and replaced in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

.

Types

In January 2011 human B1 cells were found to have marker profile of CD20+CD27+CD43+CD70- and could either be CD5+ or CD5-. CD5-CD72 is thought to mediate B cell-B cell interaction. 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 B-1a and B-1b precursors have been reported to differ in the expression levels of CD138.

Recent functional studies indicate a further subdivision of labor assigning B1a cells as the precursors 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
Borrelia hermsii is a species of Borrelia.It can be associated with relapsing fever.It can infect Ornithodoros hermsi....

and Streptococcus pneumoniae
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...

. These studies indicate preexisting subset differences in B cell receptor (BCR) specificity and antigen-driven B cell fate that remain important unresolved features of the system.

Role in immune response

B-1 cells express IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

 in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens. These polyspecific immunoglobulins often have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

 and are instead found predominantly in the peritoneal and pleural cavities. B-1 cells generate diversity mainly via recombinatorial recombination (there is a preferential recombination between D-proximal VH gene segments).

B-1 B cells characteristically express high levels of sIgM, demonstrable CD11b, and low levels of sIgD, CD21, CD23, and the B cell isoform of CD45R (B220). In adult mice, B-1 B cells constitute a minor fraction of the spleen and secondary lymphoid tissues but are enriched in the pleural and peritoneal cavities., B-1 B 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.

B-1 B 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. B-1 B cells sequences also show no evidence for somatic hypermutation
Somatic hypermutation
Somatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...

 (SHM), and few non-templated nucleotide (N) sequence insertions, a pattern typical of neonatal B cells. Efficient B-1 B cell development appears to be dependent on positive regulators of BCR signaling and the loss of negative regulators promotes greater accumulation of B-1 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.

B-1 B cells self-renew and spontaneously secrete IgM and IgG3 serum
Serum
Serum may refer to:*Blood serum, a component of blood which is collected after coagulation.**Antiserum, blood serum with specific antibodies for passive immunity*Serous fluid, any clear bodily fluid*any drug derived from an animal's blood or serous fluid...

 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 B-1 B cells regardless of specificity highlighting the innate-like activity of this separate B cell compartment.

Laboratory isolation

In research laboratories, B-1 B cells can be easily isolated from a mouse by injecting cell medium or PBS
Phosphate buffered saline
Phosphate buffered saline is a buffer solution commonly used in biological research. It is a water-based salt solution containing sodium chloride, sodium phosphate, and, in some formulations, potassium chloride and potassium phosphate. The buffer's phosphate groups help to maintain a constant pH...

 into the peritoneal cavity of the mouse and then draining it off via a technique mirroring diagnostic peritoneal lavage
Diagnostic peritoneal lavage
Diagnostic peritoneal lavage is a procedure where, after application of local anesthesia, a vertical skin incision is made one third of the distance from the umbilicus to the pubic symphysis. The linea alba is divided and the peritoneum entered after it has been picked up to prevent bowel...

. Cells can be identified and placed into two categories "B-1a" or B-1b" using flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

 looking for surface expression of CD19
CD19
B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...

, B220, and CD5. B-1a expresses high CD5 level, while B1b expresses low CD5 to almost-absent levels; both are CD19+ and B220+.
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