Plasma cells are antibody-secreting terminally differentiated non-dividing B cells, arising from dividing plasmablasts at various times and various locations during an immune response. The first-line defence against pathogens generates activated B cells, developing through plasmablasts into short-lived plasma cells, producing high amount of low affinity antibodies. Some of activated B cells can enter germinal centers of the lymph nodes and there to undergo clonal selection associated with somatic hypermutation and class switch recombination, thus those B cells that subsequently leave germinal centers develop into plasmablasts and plasma cells that secrete high affinity antibodies, or they become quiescent memory B cells, homing into various lymphoid tissues. A small portion of plasma cells manage to reach particular niches in the bone marrow and lymphoid tissues and become long-lived, able to produce high-affinity antibodies for years or even decades. After next stimulation by the antigen, rapid and massive clonal expansion of memory B cells generates to tenfold more plasma cells than a primary response does. Fig. 1: Schematic drawing on origin of three plasma cell types. Antibody secreting B cells (plasmablasts and plasma cells) express on their surface CD138 (syndecan 1) and CD319. Unlike plasmablasts, plasma cells lose expression of HLA-DR and CD19, and are Ki-67-. Another marker, CD27, helps to discriminate between naive B cells (CD27-), memory B cells (CD27+), and plasma cells (CD27++). Fig. 2: Analysis of human blood leukocytes isolated from buffy coats (B cell gate) using mouse monoclonal anti-human CD319 FITC (clone 162) and mouse monoclonal anti-human CD27 Pacific Blue™ (clone LT27). Plasma cells are CD319++CD27++. Selected antibodies:
Marker
Clone
Formats
CD138
MI15
purified (11-814-C100), Pacific Blue™ (ED7605), FITC (1F-814-T100, ED7219), Pacific Orange™ (PO-814-T100), PE (1P-814-T100), APC (1A-814-T100, ED7609), PerCP (PC-814-T100), PerCP-Cy™5.5 (ED7224).
CD319
162
purified (11-908-C100), FITC (1F-908-T100), PE (1P-908-T100).
CD27
LT27
purified (11-308-C100), Pacific Blue™ (PB-308-T100, ED7331), FITC (1F-308-T100, ED7332), Pacific Orange™ (PO-308-T100), PE (1P-308-T100, ED7333), PE-DyLight® 594 (T5-308-T100), APC (1A-308-T100, ED7651), PE- Cy™5 (T8-308-T100), PerCP-Cy™5.5 (T9-308-T100), PE- Cy™7 (T7-308-T100), APC- Cy™7 (T4-308-T100).
HLA-DR
MEM-12
purified (11-474-C100), Pacific Blue™ (PB-474-T100), FITC (1F-474-T100), PE (1P-474-T100, ED7020), APC (1A-474-T100), PerCP (PC-474-T100), Alexa Fluor® 700 (A7-474-T100).
L243
purified (11-690-C100), azide free (12-690-C100), Pacific Blue™ (PB-690-T100, ED7235), FITC (1F-690-T100, ED7236), Pacific Orange™ (PO-690-T100), PE (1P-690-T100, ED7237), PE-DyLight® 594 (T5-690-T100), APC (1A-690-T100), Alexa Fluor® 647 (A6-690-T100), Alexa Fluor® 700 (ED7238), PE-Cy™5 (T8-690-T100), PerCP-Cy™5.5 (T9-690-T100, ED7695), PE- Cy™7 (T7-690-T100), APC- Cy™7 (T4-690-T100).
CD19
LT19
purified (11-305-C100), biotin (1B-305-C100), Pacific Blue™ (PB-305-T100), FITC (1F-305-T100, ED7517), PE (1P-305-T100, ED7518), PE-DyLight® 594 (T5-305-T100, ED7227), APC (1A-305-T100, ED7134), PerCP (PC-305-T100), PerCP-Cy™5.5 (T9-305-T100, ED7172), Alexa Fluor® 700 (ED7099), PE- Cy™7 (T7-305-T100, ED7133), APC- Cy™7 (T4-305-T100, ED7135).
4G7
purified (11-663-C100), biotin (1B-663-C100), FITC (1F-663-T100), Pacific Orange™ (PO-663-T100), PE (1P-663-T100), PE-DyLight® 594 (T5-663-T100), APC (1A-663-T100), PerCP (PC-663-T100), PE-Cy™5 (T8-663-T100), PerCP-Cy™5.5 (T9-663-T100), Alexa Fluor® 700 (A7-663-T100), PE- Cy™7 (T7-663-T100).
Ki-67
purified (11-155-C100), Alexa Fluor® 488 (A4-155-T100), PE (1P-155-T100, ED7325), Alexa Fluor® 647 (A6-155-T100), PE- Cy™7 (T7-155-T100).
Further reading: Calame KL: Plasma cells: Finding new light at the end of B cell development. Nat Immunol. 2001 2(12) 1103-1107. Mei HE et al.: Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood 2009 113(11) 2461-2469. Auner HW et al.: The life span of short-lived plasma cells is partly determined by a block on activation of apoptotic caspases acting in combination with endoplasmic reticulum stress. Blood 2010 116(18) 3445-3455. Liew PX: The longevity of the humoral immune response: Survival of long-lived plasma cells. Akademeia 2012 2(1) ea0116. Halliley JL et al.: Long-lived plasma cells are contained within the CD19-CD38hiCD138+ subset in human bone marrow. Immunity 2015 43(1) 132-145. Tejero EM: Multiscale modeling of germinal center recapitulates the temporal transition from memory B cells to plasma cells differentiation as regulated by antigen affinity-based Tfh cell help. Front Immunol. 2021 11 620716. Tellier J and Nutt SL: The secret to longevity, plasma cell style. Nat Immunol. 2022 23 1507-1508. Koike T et al.: Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow. J Exp Med. 2023 220(2) e20221717.
Today we bring an extension to the Notch topics presented in previous blog.
Notch signaling represents one of the cornerstones of the immune system.
Anti-human CD38 clones HB7 and HIT2 were compared regarding their reactivity with particular blood cell populations.