diff --git a/CHANGELOG.md b/CHANGELOG.md
index 23495df7c..ed6eead1f 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -4,6 +4,7 @@
 
 ### Enhancements and minor changes
 * Added `NWBHDF5IO.read_nwb` convenience method to simplify reading an NWB file. @h-mayorquin [#1979](https://github.com/NeurodataWithoutBorders/pynwb/pull/1979)
+* Removed unused references to region references and builders in preparation for changes in HDMF 4.0. @rly [#1991](https://github.com/NeurodataWithoutBorders/pynwb/pull/1991)
 
 ### Documentation and tutorial enhancements
 - Added documentation example for `SpikeEventSeries`. @stephprince [#1983](https://github.com/NeurodataWithoutBorders/pynwb/pull/1983)
diff --git a/docs/source/overview_software_architecture.rst b/docs/source/overview_software_architecture.rst
index f2e3edc43..c1bf4a411 100644
--- a/docs/source/overview_software_architecture.rst
+++ b/docs/source/overview_software_architecture.rst
@@ -69,7 +69,7 @@ Builder
    * :py:class:`~hdmf.build.builders.GroupBuilder` - represents a collection of objects
    * :py:class:`~hdmf.build.builders.DatasetBuilder` - represents data
    * :py:class:`~hdmf.build.builders.LinkBuilder` - represents soft-links
-   * :py:class:`~hdmf.build.builders.RegionBuilder` - represents a slice into data (Subclass of :py:class:`~hdmf.build.builders.DatasetBuilder`)
+   * :py:class:`~hdmf.build.builders.ReferenceBuilder` - represents a reference to another group or dataset
 
 * **Main Module:** :py:mod:`hdmf.build.builders`
 
diff --git a/src/pynwb/io/core.py b/src/pynwb/io/core.py
index be9b234d8..0e0378c58 100644
--- a/src/pynwb/io/core.py
+++ b/src/pynwb/io/core.py
@@ -1,4 +1,4 @@
-from hdmf.build import ObjectMapper, RegionBuilder
+from hdmf.build import ObjectMapper
 from hdmf.common import VectorData
 from hdmf.utils import getargs, docval
 from hdmf.spec import AttributeSpec
@@ -40,19 +40,6 @@ def __init__(self, spec):
         self.map_spec('description', spec.get_attribute('notes'))
 
 
-class NWBTableRegionMap(NWBDataMap):
-
-    @ObjectMapper.constructor_arg('table')
-    def carg_table(self, builder, manager):
-        return manager.construct(builder.data.builder)
-
-    @ObjectMapper.constructor_arg('region')
-    def carg_region(self, builder, manager):
-        if not isinstance(builder.data, RegionBuilder):
-            raise ValueError("'builder' must be a RegionBuilder")
-        return builder.data.region
-
-
 @register_map(VectorData)
 class VectorDataMap(ObjectMapper):