Studies on the Tissue-Related Phenotypic Heterogeneity of Murine B Cells
Studies on the Tissue-Related Phenotypic Heterogeneity of Murine B Cells
PITER BALOGHa 0
ATTILA KUMANOVICS 0
ISTVAN JUHASZ 0
0 almmunological and Biotechnological Laboratory, University Medical School of Pdcs, Hungary; bDepartment of Dermatology, University Medical School of Debrecen , Hungary
The development of B cells is accompanied by their ability to specifically enter the peripheral lymphoid tissues. Recently, we described a novel rat monoclonal antibody (IBL-2; IgG2b/t0 reacting with a 26/29-kD heterodimeric structure of the cell surface. This mAb has been found to recognize differentially the peripheral B cells of mice depending on their tissue origin. The majority of splenic B cells as well as the mature B cells in the bone marrow were stained with this mAb, whereas the B lymphocytes isolated from LN or Peyer's patches displayed only negligible reactivity. We extended these observations by analyzing the relationship between the expression of IBL-2 antigen and L-selection on the surface of B-cell precursors in the bone marrow by multiparameter flow cytometry. Within the B220 positive compartment, a significant difference of L-selectin expression could be observed between the various IBL-2-reactive subsets. Furthermore, we investigated whether evidences for the establishment of tissueassociated phenotypic heterogeneity similar to that found in normal mice could be found upon the adoptive transfer of normal unselected splenic lymphocytes into SCID recipients (Spl-SCID). It has been found that a large part of the splenic B cells preserved their IBL-2 reactivity, whereas the LN B cells had lost the IBL-2 antigen in Spl-SCID. These data indicate that the phenotypic difference within the SCID mice may be the result of the migration of B lymphocytes from the spleen toward the lymph nodes, and the altered expression of the IBL-2 antigen correlates with this process.
B cells; spleen; bone marrow; L-selectin; IBL-2; SCID
INTRODUCTION
The spleen is a major target organ for peripheral
lymphocyte homing. Its histological architecture is
ments. This red pulp is intermingled with lymphoid
white pulp that, according to its cellular content, is
further subdivided into T- and B-cell compartments
(van Ewijk and Nieuwenhuis, 1985)
. This
considerrather complex, partly composed of erythromyeloid
able cellular and functional heterogeneity has
signifiregions containing some migrating lymphoid
elecantly hampered the understanding of how the
Corresponding author.
lymphocytes may localize to specific regions.
Whereas the splenic recirculation kinetics of both the
T and B cells have been thoroughly studied
(Stevens
et al., 1982; Pabst and Westermann, 1991; Picker and
Butcher, 1992)
, little is known about the cellular
interactions leading to their extravasation and
subsequent tissue positioning. The sinus-lining cells and,
less likely, the marginal zone macrophages in the
spleen have been reported to perform binding
functions similar to those of HEV cells
(Kraal et al., 1995;
Lyons and Parish, 1995)
. However, the adhesion of of
lymphocytes to either of these cells in the spleen
appears to be independent of the L-selectin or c4/37
molecules, the characteristic leukocyte structures for
binding to HEV in the lymph nodes and mucosal
lymphoid tissues, respectively
(Picker and Butcher,
1992; Bradley et al., 1994)
. It is worthwhile to
mention that the splenic but not the bone marrow
homing of myeloid precursors has proved to be
independent of the interactions between the VCAM-1
and VLA-4 molecules
(Papayannopoulou et al.,
1995)
.
The details of the in situ migration of lymphocytes
subsequent to the extravasation are also largely
unknown. It is supposed that various polysaccharides
produced by microenvironmental elements may
contribute to the lymphoid organization of the spleen
(Parish and Snowden, 1985; Kraal et al., 1994)
. On
the other hand, it is not only the microenvironment
that influences the lymphocyte migration, but the
presence of certain lymphoid elements can also
modulate the composition of the mesenchymal
scaffolding, according to the results obtained in SCID
mice
(Yoshida et al., 1993)
. Under normal
circumstances, the splenic entry of lymphocytes can be
divided into two subsequent parts. The extravasation
into the red pulp is independent from
G-proteincoupled lymphocyte membrane components inhibited
by pertussis toxin (PTX), whereas the subsequent
migration of T and B lymphocytes from the red pulp
toward the various compartments of white pulp is
likely to be mediated by PTX-sensitive structures
(Cyster and Goodnow, 1995)
. It is also not known
whether what kind of phenotypic alterations take
place in the lymphocytes upon their splenic lodging or
return from the spleen to the circulation.
We have recently reported the isolation and
characterization of a novel rat monoclonal antibody
IBL-2. This mAb reacts with the mature B cells
(identified as lg-positive cells) purified from spleen or
bone mar (...truncated)