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B1 cell
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<h2 id="origin">Origin</h2> <p>B1 cells are first produced in the <a href="/facts/Fetus/evocHd0Y">fetus</a> and most B1 cells undergo self-renewal in the periphery, unlike conventional B cells (<a href="/facts/B_cell/6Y1tgwwp">B2 cells</a>) that are produced after birth and replaced in the <a href="/facts/Bone_marrow/4dfudk0H">bone marrow</a>. </p> <h2 id="types">Types</h2> <p>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.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> 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.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> 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.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>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 <i><a href="/facts/Borrelia_hermsii/PQJsHewN">Borrelia hermsii</a></i><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> and <i><a href="/facts/Streptococcus_pneumoniae/B5XxK27j">Streptococcus pneumoniae</a></i>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> These studies indicate preexisting subset differences in <a href="/facts/B-cell_receptor/J6qRYYkN">B-cell receptor</a> (BCR) specificity and antigen-driven B cell fate that remain important unresolved features of the system. </p><p>B1a derived cells have a subset named innate response activator(IRA) B cells. IRA B cells produce <a href="/facts/GM-CSF/U15M21QE">GM-CSF</a> and <a href="/facts/Interleukin-3/mXKTzRve">IL-3</a>. In <a href="/facts/Atherosclerosis/WIS8QQ6v">atherosclerosis</a>, they accumulate in <a href="/facts/Spleen/6NKn9d8s">spleen</a>. This results in extramedullary <a href="/facts/Hematopoiesis/VRDwMymd">hematopoiesis</a> and activating <a href="/facts/Dendritic_cell/19KBuKFK">dendritic cell</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h2 id="role-in-immune-response">Role in immune response</h2> <p>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.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p><p>B1 cells express <a href="/facts/IgM/23PjpgIQ">IgM</a> in greater quantities than <a href="/facts/Immunoglobulin_G/cKzc83tk">IgG</a> and its receptors show polyspecificity, meaning that they have low affinities for many different <a href="/facts/Antigens/9JlAernG">antigens</a>. These polyspecific immunoglobulins often have a preference for other <a href="/facts/Immunoglobulins/MX8pdTdP">immunoglobulins</a>, self antigens and common bacterial polysaccharides. B1 cells are present in low numbers in the <a href="/facts/Lymph_nodes/vkwfcQjH">lymph nodes</a> and <a href="/facts/Spleen/6NKn9d8s">spleen</a> and are instead found predominantly in the <a href="/facts/Peritoneal_cavity/rSFbPzn1">peritoneal</a> and <a href="/facts/Pleural_cavity/Wel4Tz7p">pleural cavities</a>. B1 cells generate diversity mainly via recombinatorial recombination (there is a preferential recombination between D-proximal VH gene segments). </p><p>B1 cells characteristically express high levels of surface <a href="/facts/IgM/23PjpgIQ">IgM</a> (sIgM), demonstrable CD11b, and low levels of surface <a href="/facts/IgD/ASxlMgyy">IgD</a> (sIgD), CD21, CD23, and the B cell isoform of CD45R (B220).<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> 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.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a>,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> 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. </p><p>B1 cells express a separable BCR repertoire.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> Sequence analysis indicates antibodies with restricted sets of V region genes and an increased usage of λ light chains.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> B1 cells sequences also show no evidence for <a href="/facts/Somatic_hypermutation/6xXQSNsY">somatic hypermutation</a> (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.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> Hence, there appears to be a role for self or foreign antigen in shaping the repertoire of the B-1 B cell compartment.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p><p>B1 cells self-renew and spontaneously secrete IgM and IgG3 <a href="/facts/Serum_(blood)/a22tvug9">serum</a> antibodies. These natural serum antibodies display extensive polyreactivity, demonstrable self-reactivity and bind to many common pathogen-associated carbohydrates.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> 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. </p><p>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.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p><p>B1b cells have effective and long-lasting responses to <i><a href="/facts/Borrelia_hermsii/PQJsHewN">Borrelia hermsii</a></i>, <i><a href="/facts/Streptococcus_pneumoniae/B5XxK27j">Streptococcus pneumoniae</a></i>, <i>Salmonella Enterica</i>, <i><a href="/facts/Salmonella_Typhi/aj5Ax3uG">Salmonella Typhi</a></i> and <i><a href="/facts/Enterobacter_cloacae/DbVRzM5d">Enterobacter cloacae</a></i> bacteria.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p> <h2 id="laboratory-isolation">Laboratory isolation</h2> <p>In research laboratories, B1 cells can be easily isolated from a mouse by injecting cell medium or <a href="/facts/Phosphate_buffered_saline/m2gM230C">PBS</a> into the peritoneal cavity of the mouse and then draining it off via a technique mirroring <a href="/facts/Diagnostic_peritoneal_lavage/MH26fAKD">diagnostic peritoneal lavage</a>. Cells can be identified and placed into two categories "B1a" or B1b" using <a href="/facts/Flow_cytometry/M2IvPdL8">flow cytometry</a> looking for surface expression of <a href="/facts/CD19/zs1uF4S3">CD19</a>, <a href="/facts/B220/C2dU3eSd">B220</a>, and CD5. B1a expresses high CD5 level, while B1b expresses low CD5 to almost-absent levels; both are CD19+ and B220low/-. </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM (2004). "B1b lymphocytes confer T cell-independent long-lasting immunity". Immunity. 21 (3): 379–90. doi:10.1016/j.immuni.2004.06.019. PMID 15357949. <a href="https://doi.org/10.1016%2Fj.immuni.2004.06.019" target="_blank">https://doi.org/10.1016%2Fj.immuni.2004.06.019</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Griffin DO, Holodick NE, Rothstein TL (2011). "Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+ CD43+ CD70-". The Journal of Experimental Medicine. 208 (1): 67–80. doi:10.1084/jem.20101499. PMC 3023138. PMID 21220451. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023138" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023138</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Tung JW, Mrazek MD, Yang Y, Herzenberg LA, Herzenberg LA (2006). "Phenotypically distinct B cell development pathways map to the three B cell lineages in the mouse". Proceedings of the National Academy of Sciences of the United States of America. 103 (16): 6293–8. Bibcode:2006PNAS..103.6293T. doi:10.1073/pnas.0511305103. PMC 1458871. PMID 16606838. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458871" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458871</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM (2004). "B1b lymphocytes confer T cell-independent long-lasting immunity". Immunity. 21 (3): 379–90. doi:10.1016/j.immuni.2004.06.019. PMID 15357949. <a href="https://doi.org/10.1016%2Fj.immuni.2004.06.019" target="_blank">https://doi.org/10.1016%2Fj.immuni.2004.06.019</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Haas KM, Poe JC, Steeber DA, Tedder TF (2005). "B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae". Immunity. 23 (1): 7–18. doi:10.1016/j.immuni.2005.04.011. PMID 16039575. <a href="https://doi.org/10.1016%2Fj.immuni.2005.04.011" target="_blank">https://doi.org/10.1016%2Fj.immuni.2005.04.011</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Chousterman, Benjamin G.; Swirski, Filip K. (2015-05-08). "Innate response activator B cells: origins and functions". International Immunology. 27 (10): 537–541. doi:10.1093/intimm/dxv028. ISSN 0953-8178. PMC 4693688. PMID 25957266. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693688" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693688</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Ghosn EE, Yang Y, Tung J, Herzenberg LA, Herzenberg LA (2008). "CD11b expression distinguishes sequential stages of peritoneal B-1 development". Proceedings of the National Academy of Sciences of the United States of America. 105 (13): 5195–200. Bibcode:2008PNAS..105.5195G. doi:10.1073/pnas.0712350105. PMC 2278228. PMID 18375763. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278228" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278228</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Hayakawa K, Hardy RR, Herzenberg LA, Herzenberg LA (1985). "Progenitors for Ly-1 B cells are distinct from progenitors for other B cells". The Journal of Experimental Medicine. 161 (6): 1554–68. doi:10.1084/jem.161.6.1554. PMC 2187623. PMID 3874257. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2187623" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2187623</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Lalor PA, Stall AM, Adams S, Herzenberg LA (1989). "Permanent alteration of the murine Ly-1 B repertoire due to selective depletion of Ly-1 B cells in neonatal animals". 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Annual Review of Immunology. 11: 501–38. doi:10.1146/annurev.iy.11.040193.002441. PMID 8476571. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Cunningham AF, Flores-Langarica A, Bobat S, Medina CC, Cook CN, Ross EA, Lopez-Macias C, Henderson IR (2014). "B1b cells recognize protective antigens after natural infection and vaccination". Front Immunol. 5 (535): 379–90. doi:10.3389/fimmu.2014.00535. PMC 4215630. PMID 25400633. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215630</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> </ol>