B-cell subsets in blood and lymphoid organs in Macaca fascicularis.
BACKGROUND
Cynomolgus monkeys (Macaca fascicularis) are widely used animal models in biomedical research. However, the phenotypic characteristics of cynomolgus monkey (CM) B cells in peripheral blood (PB) and lymphoid organs are poorly understood.


METHODS
FACS analyses of PB-, spleen-, lymph node (LN)-, and bone marrow (BM)-derived B cells were performed.


RESULTS
CM peripheral blood B cells have a smaller fraction of CD27(-) (naive) cells ( approximately 40%), as compared to human blood samples ( approximately 70%). Similar to humans, an early activation marker, CD23, is expressed more on CD27(-) CM naive B cells, as compared to CD27(+) B cells. The mean fraction of B cells exhibiting a memory phenotype is similar to that seen in human blood. Unlike humans, CM blood contains a subset of CD20(++)CD80(+)CD21(-)IgM(+/-)CD27(+)CD19(+)FSC(++)BAFF-R(low) B cells that are likely of germinal center origin. Thus, CM blood contains (i) a higher percentage of B cells that express the co-stimulatory molecule CD80, and (ii) a lower fraction of B cells that are CD21(+), as compared to human blood. Due to the relative paucity of information on B-cell subsets in organs of healthy humans, a direct comparison between human and CM lymphoid organ data is limited. The fraction of CD27(+) and CD23(+) B cells appears to be similar, while the fraction of CD80(+) B cells appears to be higher than that seen in human lymphoid organs. CM spleens and to some extent lymph nodes have a distinct subset of CD21(++) cells that are also CD80(+/-)CD23(low)IgM(++)CD27(+/-)FSC(++). This subset is phenotypically similar to the marginal zone B cells present in human spleen and LN samples. We also provide detailed analyses on the fraction of lymphoid organ B cells that express CD21, CD23, CD32, and/or CD80 B-cell markers.


CONCLUSIONS
In general, cynomolgus monkey B-cell subsets are similar to those seen in humans, as well as to those seen in other nonhuman primates. However, there are some clear differences between human and cynomolgus monkey B-cell subsets. These findings have direct implications for a variety of in vivo studies in cynomolgus monkeys, ranging from basic research on primate B-cell differentiation to models of infectious diseases and trials of new B-cell targeting therapeutic agents.
Vugmeyster
Y
Y
Bioanalytical Research and Development, Genentech Inc., South San Francisco, California, USA. yulia@gene.com
Howell
K
K
Bakshi
A
A
Flores
C
C
Hwang
O
O
McKeever
K
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology*; D008252:Macaca fascicularis / Q000276:immunology*
D015703:Antigens, CD