B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells.

The production and release of small phospholipid membrane vesicles, or extracellular vesicles (EVs), is a trait of most prokaryotic and eukaryotic cells. EVs display heterogeneity in content, size, biogenesis, activity, and function. B cells uniquely express immunoglobulin and produce EVs; however, the relationship between these entities has not been clarified.

Age-related changes in antigen-specific natural antibodies are influenced by sex.

Introduction: Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis.

B-1b Cells Have Unique Functional Traits Compared to B-1a Cells at Homeostasis and in Aged Hyperlipidemic Mice With Atherosclerosis.

Immunoglobulin M (IgM) to oxidation specific epitopes (OSE) are inversely associated with atherosclerosis in mice and humans. The B-1b subtype of B-1 cells secrete IgM to OSE, and unlike B-1a cells, are capable of long-lasting IgM memory. What attributes make B-1b cells different than B-1a cells is unknown.

Modulation of microbiome diversity and cytokine expression is influenced in a sex-dependent manner during aging.

The microbiome and immune system have a unique interplay, which influences homeostasis within the organism. Both the microbiome and immune system play important roles in health and diseases of the aged including development of cancer, autoimmune disorders, and susceptibility to infection. Various groups have demonstrated divergent changes in the gut microbiota during aging, yet the compounding factor of biological sex within the context of aging remains incompletely understood, and little is known about the effect of housing location in the composition of gut microbiota in the context of both sex and age.

Antigen Receptor Specificity and Cell Location Influence the Diversification and Selection of the B-1a Cell Pool with Age.

B-1a cells provide immediate and essential protection from infection through production of natural Ig, which is germline-like due to minimal insertion of N region additions. We have previously demonstrated peritoneal B-1a cell-derived phosphorylcholine-specific and total IgM moves away from germline (as evidenced by an increase in N-additions) with age as a result of selection. In young mice, anti-phosphatidylcholine Abs, like anti-phosphorylcholine Abs, contain few N-additions, and have been shown to be essential in protection from bacterial sepsis.

Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked to Human Coronary Atherosclerosis.

Rationale: B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining the BM B-1a population remain unexplored. CXCR4 (C-X-C motif chemokine receptor 4) has been implicated in human cardiovascular disease and B-cell homeostasis, yet the role of B-1 cell CXCR4 in regulating atheroprotective IgM levels and human cardiovascular disease is unknown.

B-1a cells protect mice from sepsis-induced acute lung injury.

Background: Sepsis morbidity and mortality are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Mouse B-1a cells are a phenotypically and functionally unique sub-population of B cells, providing immediate protection against infection by releasing natural antibodies and immunomodulatory molecules. We hypothesize that B-1a cells ameliorate sepsis-induced ALI.

Defining Natural Antibodies.

The traditional definition of natural antibodies (NAbs) states that these antibodies are present prior to the body encountering cognate antigen, providing a first line of defense against infection thereby, allowing time for a specific antibody response to be mounted. The literature has a seemingly common definition of NAbs; however, as our knowledge of antibodies and B cells is refined, re-evaluation of the common definition of Nabs may be required. Defining Nabs becomes important as the function of NAb production is used to define B cell subsets (1) and as these important molecules are shown to play numerous roles in the immune system (Figure 1).

CD25 B-1a Cells Express .

B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID), a product of the gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for in B-1a cells has been suggested on the basis of experiments with knock out (KO) mice, whether B-1a cells express , and if so, which B-1a cell subpopulation expresses , remains unknown.

B-1a Cells Protect Mice from Sepsis: Critical Role of CREB.

Bacterial sepsis is a serious life-threatening condition caused by an excessive immune response to infection. B-1 cells differ from conventional B-2 cells by their distinct phenotype and function. A subset of B-1 cells expressing CD5, known as B-1a cells, exhibits innate immune activity.

B-CD8 T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody.

P3 is a murine, germline, IgM mAb that recognizes -glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo.

Human B-1 and B-2 B Cells Develop from Lin-CD34+CD38lo Stem Cells.

The B-1 B cell population is an important bridge between innate and adaptive immunity primarily because B-1 cells produce natural Ab. Murine B-1 and B-2 cells arise from distinct progenitors; however, in humans, in part because it has been difficult to discriminate between them phenotypically, efforts to pinpoint the developmental origins of human B-1 and B-2 cells have lagged. To characterize progenitors of human B-1 and B-2 cells, we separated cord blood and bone marrow LinCD34 hematopoietic stem cells into LinCD34CD38 and LinCD34CD38 populations.

Blood pressure regulation by CD4 lymphocytes expressing choline acetyltransferase.

Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4 T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4CD44CD62L T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T).

Age-Related Decline in Natural IgM Function: Diversification and Selection of the B-1a Cell Pool with Age.

Streptococcus pneumoniae is the most common cause of pneumonia, which claims the lives of people over the age of 65 y seven times more frequently than those aged 5-49 y. B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural Ig, which has minimal insertion of N-region additions added by the enzyme TdT.

Expansion of B-1a Cells with Germline Heavy Chain Sequence in Lupus Mice.

B6.Sle1.Sle2.

The role of B-1 cells in inflammation.

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire-skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules such as interleukin-10, adenosine, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases.

Analysis of IgM antibody production and repertoire in a mouse model of Sjögren's syndrome.

This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjögren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjögren's syndrome mouse model (Id3(-/-)). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells.

B cells in the aging immune system: time to consider B-1 cells.

The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence.

Splenic B-1a Cells Expressing CD138 Spontaneously Secrete Large Amounts of Immunoglobulin in Naïve Mice.

B-1a cells constitutively secrete natural antibody that provides immediate protection against microbial pathogens and functions homeostatically to speed removal of apoptotic cell debris. Although B-1a cells are especially prominent in the peritoneal and pleural cavities, some B-1a cells reside in the spleen. A small subset of splenic B-1a cells in naïve, unimmunized mice express CD138, a recognized plasma cell antigen, whereas the bulk of splenic B-1a cells are CD138 negative.

B-1a cell diversity: nontemplated addition in B-1a cell Ig is determined by progenitor population and developmental location.

Natural Abs produced by B-1a cells are required for immediate protection against infection. The protective capacity of natural Abs is attributed to germline-like structure, which includes the relative absence of N-region addition. Previous studies have shown B-1a cell Ig from aged mice contains abundant nontemplated (N)-additions.

Atypical Response of B-1 Cells to BCR Ligation: A Speculative Model.

Peritoneal B-1a cells manifest unusual signaling characteristics that distinguish them from splenic B-2 cells. These include the failure of BCR engagement to trigger NF-κB activation and DNA replication. Despite extensive study, a clear explanation for these characteristics has not emerged.